Cross references: Salamander Brain Downloads Salamander Brain Diagram Salamander Brain Illustrations Salamander Brain Text Salamander Brain OCR Salamander Dominance Hierarchies Salamander http://www.biodiversitylibrary.org/ The brain of the tiger salamander, Ambystoma tigrinum. Chicago,Univ. of Chicago Press[1948] http://www.biodiversitylibrary.org/bibliography/6375 Item: http://www.biodiversitylibrary.org/item/28763 Page(s): Cover, Text, Text, Text, Text, Text, Text, Text, Title Page, Text, Text, Text, Table of Contents, Text, Page 1, Page 2, Page 3, Page 4, Page 5, Page 6, Page 7, Page 8, Page 9, Page 10, Page 11, Page 12, Page 13, Page 14, Page 15, Page 16, Page 17, Page 18, Page 19, Page 20, Page 21, Page 22, Page 23, Page 24, Page 25, Page 26, Page 27, Page 28, Page 29, Page 30, Page 31, Page 32, Page 33, Page 34, Page 35, Page 36, Page 37, Page 38, Page 39, Page 40, Page 41, Page 42, Page 43, Page 44, Page 45, Page 46, Page 47, Page 48, Page 49, Page 50, Page 51, Page 52, Page 53, Page 54, Page 55, Page 56, Page 57, Page 58, Page 59, Page 60, Page 61, Page 62, Page 63, Page 64, Page 65, Page 66, Page 67, Page 68, Page 69, Page 70, Page 71, Page 72, Page 73, Page 74, Page 75, Page 76, Page 77, Page 78, Page 79, Page 80, Page 81, Page 82 Contributed by: MBLWHOI Library, Woods Hole Sponsored by: MBLWHOI Library Generated 31 March 2012 4:48 PM http://www.biodiversitylibrary.org/pdf3/010207400028763 This page intentionally left blank. The following text is generated from uncorrected OCR. [Begin Page: Cover] [Begin Page: Text] [Begin Page: Text] : m ' CO I <=o r-=| O o [Begin Page: Text] [Begin Page: Text] THE BRAIN OF THE TIGER SALAMANDER [Begin Page: Text] [Begin Page: Text] [Begin Page: Text] The tiger salamander, Ambystoma tigrinum, natural size. The figure at the top is a midwestern adult form, after G. K. Noble ('31, by permission of the McGraw-Hill Book Co.). Below this is a photograph of a midlarval stage by Professor S. H. Bishop. The two lower figures show late larval and adult stages of the eastern form, the adult with brilliant yellow "tiger" stripes. (Courtesy of the American Museum of Natural History.) [Begin Page: Title Page] THE BRAIN OF THE TIGER SALAMANDER Amby stoma tigrinum By C. JUDSON HERRICK Professor Emeritus of Neurology The University of Chicago > THE UNIVERSITY OF CHICAGO PRESS CHICAGO • ILLINOIS \ [Begin Page: Text] THE UNIVERSITY OF CHICAGO COMMITTEE ON PUBLICATIONS IN BIOLOGY AND MEDICINE LESTER R. DRAGSTEDT • R. WENDELL HARRISON FRANKLIN C. McLEAN • C. PHILLIP MILLER THOMAS PARK • WILLIAM H. TALIAFERRO The University of Chicago Press, Chicago 37 Cambridge University Press, London, N.W. 1, England W. J. Gage & Co., Limited, Toronto '2B, Canada Copyright 19^8 by The University of Chicago. All rights reserved Published 191,8. Composed and printed by The University OF Chicago Press, Chicago, Illinois, U.S.A. [Begin Page: Text] PREFACE THIS work reports the results of a search, extending over fifty years, for the fundamental plan of the vertebrate nervous system as revealed in generalized form in the amphibians. In these small brains we find a simplified arrangement of nerve cells and fibers with a pattern of structural organization, the main features of which are common to all vertebrates. From this primitive and relatively unspecialized web of tissue it is possible to follow the successive steps in progressive elaboration as the series of animals from salamanders to men is passed in review. This is a record of personal observation, not a compilation of the literature. It is presented in two parts, which differ in content and method of treatment of the data. The first part gives a general over-all view of the structure without details, followed by physiological interpretation and discussion of some general principles of embryologic and phylogenetic morphogenesis. This part, with the accompanying illustrations, can be read independently of the histological details recorded in the second part. The second part presents the evidence upon which conclusions are based, drawn from my own previously published descriptions, to which references are given, together with considerable new material. This part is designed for specialists in comparative neurology and as a guide for physiological experiments. The second part supplements the first, to which the reader must make frequent reference. Grateful acknowledgment is made to many colleagues for generous assistance and criticism, and particularly to Doctors Elizabeth C. Crosby, Davenport Hooker, Olof Larsell, Gerhardt von Bonin, Ernst Scharrer, and W. T. Dempster. In the preparation of the manuscript invaluable help was given by Miss Anna Seaburg. I am indebted to Dr. Paul G. Roofe for permission to copy one of his pictures, shown here as figure 86A. The American Museum of Natural History, New York, generously furnished the two photographs, taken from life, shown at the bottom of the Frontispiece. These are copyrighted by the Museum. One of them has been previously published by the Macmillan Company in Hegner's Parade [Begin Page: Text] vi PREFACE of the Animal Kingdom (p. 289). The photograph of the midlarval stage was kindly suppHed by Professor Sherman C. Bishop of the University of Rochester. The upper figure is from G. K. Noble's Biology of the Amphibia, courtesy of the McGraw-Hill Book Company (copyrighted, 1931). Figures 1, 2C, and 86-113 are reproductions of figures previously published by the author in the Journal of Comparative Neurology and used here by courtesy of the Wistar Institute of Anatomy and Biology, publishers of that Journal. The other figures are originals prepared for this work. Money for the prosecution of the work and for financing its publication was liberally supplied by the Dr. Wallace C. and Clara A. Abbott Memorial Fund of the University of Chicago. [Begin Page: Table of Contents] CONTENTS PART I. GENERAL DESCRIPTION AND INTERPRETATION I. Salamanders and Their Brains JJ The salamanders, 3. — The scope of this inquiry, 4. — The plan of this book, 6.— Sources and material, 10.— Development of the brain, 11. — The evolution of brains, 13 II. The Form and Subdivisions of the Brain 18 Gross structure, 18.— Ventricles, "24.— Meninges, chorioid plexuses, and blood vessels, 'id III. Histological Structure '28 General histology, 38.— The neuropil, '29.— The ventrolateral peduncular neuropil, 3,3 IV. Regional Analysis 4<> The subdivisions, spinal cord to pallium, 41.— The commissures, ;5;5. ^Conclusion, 56 V. Functional Analysis, Central and Peripheral 57 The longitudinal zones, 57. — The sensory zone, 58. — The motor zone, 60. — The intermediate zone, 64.— The functional systems, 65 VI. Physiological Interpretations '^^ Apparatus of analysis and synthesis, 70. — The stimulus-response formula, 7^2. — Reflex and inhibition, 73.— Principles of localization of function, 8'2 Vll. The Origin and Significance of Cerebral Cortex .... 91 The problem, 91. — Morphogenesis of the cerebral hemispheres, 9*2. — The cortex, 98. — Physiology and psychology, 106 VIII. General Principles of Morphogenesis 109 Morphogenic agencies, 109. — Morphological landmarks, 116. — The future of morphology, 120 PART II. SUR\^Y OF INTERNAL STRUCTURE IX, Spinal Cord and Bulbo-spinal Junction 1'25 The spinal cord and its nerves, 125. — The bulbo-spinal junction, 129 X. Cranial Nerves l-^l Development, 131. — Survey of the functional systems, 132 XI. Medulla Oblongata ^^'^ Sensory zone, 153. — Intermediate zone, 156. — Motor zone, 157. — Fiber tracts of the medulla oblongata, 158.— The lemniscus sy.stems, 162 vii 63291 [Begin Page: Text] viii CONTENTS XII. Cerebellum ^'^ Brachium conjunctivum, 176.— The cerebellar commissures, 177.— Proprioceptive functions of the cerebellum, 178 XIII. Isthmus 1'^^ Development, 179.— Sensory zone, 181.— Intermediate zone, 182. —Motor zone, 182.— White substance, 186.— Isthmic neuropil, 187. — Physiological interpretation, 189 XIV. Interpeduncular Nucleus l^^ Comparative anatomy, 191.— Histological structure, 193.— Afferent connections, 197.— Efferent connections, 201.— Interpretation, 202. — Conclusion, 210 XV. Midbrain ^^'^ Development, 212.— Sensory zone, 214.— Intermediate zone, 215. — Motor zone, 216 XVI. Optic and Visual-motor Systems 219 Optic nerve and tracts, 219.— Tectum opticum, 222.— Tectooculomotor connections, 226.— Visual functions, 227 XVII. Diencephalon ^^^ General features, 230.— Development, 231.— Epithalamus, 234.— Dorsal thalamus, 236.— Ventral thalamus.— 239.— Hypothalamus, 241 XVIII. The Habenula and Its Connections 247 The di-telencephalic junction, 247.— Fornix, 254.— Stria terminalis, 255.— Stria medullaris thalami, 256.— Fasciculus retroflexus, 261 XIX. The Cerebral Hemispheres 265 Subdivisions of the hemisphere, 265.— The olfactory system, 266 XX. The Systems of Fibers 270 The basal forebrain bundles, 271.— The tegmental fascicles, 275.— Fasciculus tegmentalis profundus, 286 XXI. The Commissures ^^^ General considerations, 289.— The dorsal commissures, 292.— The ventral commissures, 294 BIBLIOGRAPHY ILLUSTRATIONS *?07 Bibliography Illustrations ABBREVIATIONS FOR ALL FIGURES Abbreviations for All Figures ^^^ INDEX Index ^99 [Begin Page: Page 1] PART I GENERAL DESCRIPTION AND INTERPRETATION [Begin Page: Page 2] [Begin Page: Page 3] CHAPTER I SALAMANDERS AND THEIR BRAINS THE SALAMANDERS SALAMANDERS are shy little animals, rarely seen and still more rarely heard. If it were not so, there would be no salamanders at all, for they are defenseless creatures, depending on concealment for survival. And yet the tiger salamander, to whom this book is dedicated, is appropriately named, for within the obscurity ol its contracted world it is a predaceous and voracious terror to all humbler habitants. This salamander and closely allied species have been found to be so well adapted for a wide range of studies upon the fundamental features of growth and differentiation of animal bodies that during the last fifty years there has been more investigation of the structure, development, and general physiology of salamanders than has been devoted to any other group of animals except mankind. The reason for this is that experimental studies can be made with these amphibians that are impossible or much more difficult in the case of other animals. This is our justification for the expenditure of so much hard work and money upon the study of the nervous system of these insignificant little creatures. The genus Amby stoma is widely distributed throughout North America and the tiger salamander, A. tigrinum, is represented by several subspecies. The individuals vary greatly in size and color, and the subspecies have different geographical distribution, with some overlap of range (Bishop, '43). The subspecies, A. tigrinum tigrinum (Green), ranges from New York southward to Florida and westward to Minnesota afid Texas. It has a dark-brown body crossed by bright-yellow stripes, as shown in the lower figure of the Frontispiece. The species probably was named for these tiger-like markings, not for its tigerish ferocity. The upper figure of the Frontispiece is an adult of a western form, with less conspicuous markings. Other subspecies range as far to the northwest as Oregon and British Columbia. Several other species of Ambystoma are found in the same areas as A. tigrinum. 3 [Begin Page: Page 4] 4 THE BRAIN OF THE TIGER SALAMANDER Zoological names. — The approved names of the genus and larger groups to which reference is here made, as given in a recent official list (Pearse, '36), are as follows: Salienta, to replace Anura Caudata, to replace Urodela Ambystoma, to replace Amblystoma Amby stoma (or Siredon) maculatum has priority over A. punctatum. The names, Anura, Urodela, and Amblystoma, are used throughout this text because they are so commonly found in current literature that they may be regarded as vernacular terms. THE SCOPE OF THIS INQUIRY From the dawn of interest in the minute structure of the human brain, it was recognized that the simpler brains of lower vertebrates present the fundamental features of the human brain without the numberless complications which obscure these fundamentals in higher animals. This idea motivated much research by the pioneers in neuroanatomy, and it was pursued systematically by L. Edinger, H. Obersteiner, Ramon y Cajal, C. L. Herrick, J. B. Johnston, Ariens Kappers, and many others. In 1895, van Gehuchten wrote that he was engaged upon a monograph on the nervous system of the trout, "impressed by the idea that complete information about the internal organization of the central nervous system of a lower vertebrate would be of great assistance as our guide through the complicated structure of the central nervous system of mammals and of man." The few chapters of this monograph which appeared before his untimely death intensify our regret that he was not permitted to complete this work. Van Gehuchten's ideal has been my own inspiration. Our primary interest in this inquiry is in the origins of the structural features and physiological capacities of the human brain and the general principles in accordance with which these have been developed in the course of vertebrate evolution. This is a large undertaking. What, then, is the most promising approach to it.'^ My original plan was, first, to review all that has been recorded about the anatomy and physiology of the nervous systems of backboned animals, to arrange these animals in the order of their probable diverse specialization from simple to complex in the evolutionary sequence, then to select from the series the most instructive types and subject them to intensive study, in the expectation that the principles underlying these morphological changes would emerge. So ambitious a plan, however, is far too big to be encompassed within the span of one man's lifetime. The fact-finding research is [Begin Page: Page 5] SALAMANDERS AND THEIR BRAINS 5 extremely laborious and exacting; and, during the fifty years which have elapsed since my project was formulated, the descriptive literature has increased to enormous volume. This literature proves to be peculiarly refractory to analysis and interpretation. Until recently this vast accumulation of factual knowledge has contributed disappointingly little to the resolution of the fundamental problems of human neurology. Nevertheless, the method is sound, and this slow growth is now coming to fruition, thanks to the conjoint labors of specialists in many fields of science. What no individual can hope to do alone can be done and has been done in co-operative federation, as illustrated, for instance, by the Kappers, Huber, and Crosby team and their many collaborators. Traditionally, comparative neurology has been regarded as a subdivision of comparative anatomy, and so it is. But it is more than this. The most refined methods of anatomical analysis cannot reveal the things that are of greatest significance for an understanding of the nervous system. Our primary interest is in the behavior of the living body, and we study brains because these organs are the chief instruments which regulate behavior. As long as anatomy was cultivated as a segregated discipline, its findings were colorless and too often meaningless. Now that this isolationism has given way to genuine collaboration among specialists in all related fields — physiology, biochemistry, biophysics, clinical practice, neuropathology, psychology, among others — we witness today a renaissance of the science of neurology. The results of the exacting analytic investigations of the specialists can now be synthesized and given meaning. The task of comparative anatomy in this integrated program of research is fundamental and essential. The experimentalist must know exactly what he has done to the living fabric before he can interpret his experiment. In the past it too often happened that a physiologist would stab into a living frog, take his kymograph records, and then throw the carcass into the waste-jar. This is no longer regarded as good physiology. Without the guidance of accurate anatomical knowledge, sound physiology is impossible; and, without skilful physiological experimentation, the anatomical facts are just facts and nothing more. Early in my program the amphibians were selected as the most favorable animals with which to begin a survey of the comparative anatomy of the nervous system. Time has proved the wisdom of this [Begin Page: Page 6] 6 THE BRAIN OF THE TIGER SALAMANDER choice, and the study of these animals has been so fruitful that by far the larger part of my research has been devoted to them. In this work it was my good fortune to be associated with the late G. E. Coghill, whose distinguished career pointed the way to an original approach to the problems of the origins and growth of the nervous organs and their functions. The record of phylogenetic history spans millions of years and is much defaced by time; but the record of the embryonic development of the individual is measured in days and hours, and every detail of it can be watched from moment to moment. The internal operations of the growing body are not open to casual inspection, but Coghill showed us that the sequence of these changes can be followed. He selected the salamanders for his studies for very good reasons, the same reasons that led me to take these animals as my own point of departure in a program of comparative neurology. My intimate association with Coghill lasted as long as he lived, and the profound influence which his work has had upon the course of biological and psychological events in our generation has motivated the preparation of a book devoted to his career ('48). This influence, though perhaps unrecognized at the time, was doubtless largely responsible for my persistent efforts to analyze the texture of the amphibian nervous system, for his studies of the growth of patterns of behavior and their instrumentation in young stages of salamanders brought to light some prmciples which evidently are applicable in phylogenetic development also. While Coghill's studies on the development of salamanders were in process, we were impressed by the importance of learning just how these processes of growth eventuate in the adult body. This was my job, and so we worked hand in hand, decade after decade, for forty years. Progress was slow, but our two programs fitted together so helpfully that my original plan for a comprehensive study of the comparative anatomy of the nervous system was abandoned in favor of more intensive study of salamanders. THE PLAN OF THIS BOOK The preceding details of personal biography are relevant here because they explain the motivation and plan of this book. The significant facts now known about the internal structure of the brain of the tiger salamander in late larval and adult stages are here assembled. The observation's on this and allied species previously re[ Begin Page: Page 7] SALAMANDERS AND THEIR BRAINS 7 corded by the writer and many others are widely scattered, often in fragmentary form, and with confusing diversity in nomenclature and interpretation. As observations have accumulated, gaps in knowledge have been filled, early errors have been corrected, the nomenclature has been systematized, and now, with the addition of considerable new observation here reported, the structure may be viewed as a whole and interpreted in relation with the action system of the living animal. Many of my observations during the last fifty years confirm those of others; and, since references to these are given in the papers cited, this account is not encumbered with them except where they supplement my own experience or deal with questions still in controversy. I here describe what I myself have seen, with exceptions explicitly noted. This explains the disproportionate number of references in the text to my own papers. Two genera of urodeles have been studied intensively to find out what is the instrumentation of their simple patterns of behavior. All observations on the brain of the more generalized mudpuppy, Necturus, were assembled in a monograph ('336) and several followmg papers. The present work is a similar report upon the brain of the somewhat more specialized tiger salamander. The original plan was to follow this with an examination of the brain of the frog, for which abundant material was assembled and preliminary surveys were made; but this research, which is urgently needed, must be done by others. In this book the anatomical descriptions are arranged in such a way as to facilitate interpretation in terms of probable physiological operation. Though the amount of experimental evidence about the functions of the internal parts of the amphibian brain is scanty, there is, fortunately, a wealth of such observation about the brains of other animals; and where a particular structural pattern is known to be colligated with a characteristic pattern of action, the structure may be taken as an indicator of the function. The reliability of this method depends upon the adequacy of our knowledge of both the function and the structure. The present task, then, is an assembly of the anatomical evidence upon which the interpretations are based. The first part of this work is written to give biologists and psychologists an outline of the plan of organization of a generalized vertebrate brain and some insight into the physiological principles exemplified in its action. These eight chapters, with the accompanying illustrations, can be read independently of the rest of the book. [Begin Page: Page 8] 8 THE BRAIN OF THE TIGER SALAMANDER Part II is written for specialists in comparative neurology. It covers the same ground as the first part, reviewing each of the conventional subdivisions of the brain, giving details of the evidence upon which conclusions are based, with references to sources and much new material. This involves some repetition, which is unavoidable because all these structures are interconnected and in action they co-operate in various ways. Many structures must be described in several contexts and, accordingly, the Index has been prepared with care so as to enable the reader to assemble all references to every topic. The most important new observations reported in Part II relate to the structure and connections of the isthmus (chap, xiii), interpeduncular nucleus (chap, xiv), and habenula, including analysis of the stria medullaris thalami and fasciculus retroflexus (chap, xviii). In chapter xx a few of the more important systems of fibers are described, including further analysis of the tegmental fascicles as enumerated in the paper of 1936 and references to other lists in the literature. The composition of the commissures of the brain is summarized in chapter xxi. The lemniscus systems are assembled in chapter xi, and other tracts are described in connection with the structures with which they are related. Since most neurologists are not expert in the comparative field, where the nomenclature is technical and frequently unintelligible except to specialists, the attempt is made in Part I to present the salient features with a minimum of confusing detail and, so far as practicable, in terms of familiar mammalian structure. This is not an easy thing to do, and no clear and simple picture can be drawn, for the texture of even so lowly organized a brain is bafflingly complicated and many of these structures have no counterparts in the human body. Homologies implied by similar names are rarely exact, and in many of these cases the amphibian structure is regarded as the undifferentiated primordium from which the mammalian has been derived. This is emphasized here because homologies are usually defined in structural terms and because organs which are phylogenetically related are regarded as more or less exactly homologous, regardless of radical changes in their functions. Thus the "dorsal island" in the acousticolateral area of the medulla oblongata of Necturus is regarded as the primordium of the dorsal cochlear nucleus of mammals, despite the fact that Necturus has no recognizable rudiment of a cochlea or cochlear nerve. This is because, when the [Begin Page: Page 9] SALAMANDERS AND THEIR BRAINS 9 cochlear rudiment and its nerve appear in the frog, the tissue of the "dorsal island" receives the cochlear nerve with radical change in the functions performed (p. 138). The histological texture of these brains is so different from that of mammalian brains that the development of an intelligible nomenclature presents almost insuperable difficulty — a difficulty exacerbated by the fact that in the early stages of the inquiry it was necessary to apply descriptive terms to visible structures before their relationships were known. With increase of knowledge, errors were corrected, and unsuitable names were discarded; but terms already in use are still employed so far as possible, even though they are in some cases cumbersome and now known to be inappropriate. In all these descriptions I have consistently used the word "fissure" to designate visible furrows on the external surface of the brain and "sulcus" for those on ventricular surfaces. Attention is called to the list of abbreviations (p. 391) and to previous lists there cited where synonyms are given. In all my published figures of brains of urodeles the intent has been to use the same abbreviations for comparable structures. This intention has been approximately realized, but there are some inconsistencies, in most of which the differences express a change in emphasis rather than a correction of errors of observation. Many well-defined tracts of fibers seen in fishes and higher animals are here represented in mixed collections of fibers of diverse sorts, here termed "fasciculi," or they may be dispersed within a mixed neuropil. The practice here is to define as a "tract" all fibers of like origin or termination, whether or not they are segregated in separate bundles. The customary self-explanatory binomial terminology is used wherever practicable — a compound word with origin and termination separated by a hyphen. But, since a single fiber of a tract may have collateral connections along its entire length, the fully descriptive name may become unduly cumbersome ('41a, p. 491). Thus, in accordance with strict application of the binomial terminology, tractus strio-tegmentalis would become tractus striothalamicus et peduncularis et tegmentalis dorsalis, isthmi et trigemini. The chemists seem to be able to manipulate similar enormities even without benefit of hyphens or spaces, but not many anatomists are so hardy. Few of the named tracts are sharply delimited, and all of them are mixtures of fibers with different connections. Any analysis is necessarily somewhat arbitrary. Simple action systems of total-pattern type, wherever found 2j;. LIBRARY] [Begin Page: Page 10] 10 THE BRAIN OF THE TIGER SALAMANDER (cyclostomes, primitive ganoid fishes, urodeles), are correlated with a histological texture of the brain which is characteristic and probably primitive (chap. iii). The external configuration of the urodele brain also is generalized, much as in a human embryo of about 6 weeks. In the next chapter special attention is directed to this comparison to assist the reader in identifying familiar parts of the human brain as they are seen in the simplified amphibian arrangement. In our comparison of the amphibian brain with the human, two features are given especial emphasis, both of which are correlated with differences in the mode of life of the animals in question, that is, with the contrast between the amphibian simplicity of behavior with stereotyped total patterns of action predominating and the human complexity of movement in unpredictable patterns. The correlated structural differences are, first, in Amblystoma the more generalized histological texture to which reference has just been made, and notably the apparent paucity of provision for well-defined localization of function in the brain; and, second, the preponderant influence of motor patterns rather than sensory patterns in shaping the course of differentiation from fishlike to quadrupedal methods of locomotion and somatic behavior in general. SOURCES AND MATERIAL The material studied comprises gross dissections and serial sections of about five hundred specimens of Amblystoma from early embryonic to adult stages. About half these brains were prepared by the Golgi method and the remainder by various other histological procedures. Most of these are A. tigrinum, some are A. maculatum (punctatum), and a few are A. jeffersonianum. In early developmental stages some specific differences have been noted in the embryological papers of 1937-41, but no systematic comparative study has been made. The late larval and adult brains under consideration in this book are of A. tigrinum. In former papers there are comments on this material and the methods of preparation ('25, p. 436; '35a, p. 240; '42, p. 193). In the study of these sections the cytological methods of Nissl and others are less revealing than in more highly differentiated brains because of the unspecialized structure of the nervous elements. Some modifications of the method of Weigert which decolorize the tissue sufficiently to show the myelinated fibers and also the arrangement [Begin Page: Page 11] SALAMANDERS AND THEIR BRAINS 1 1 of cell bodies prove to be most useful for general orientation. Other details can then be filled in by study of reduced silver preparations and especially of Golgi sections. A favorable series of transverse Weigert sections (no. IIC; see p. 3'21) has been chosen as a type or standard of reference, and the median section as reconstructed from this specimen (fig. 2C) has been used as the basis for many diagrams of internal structure. For reference to published figures of this brain and other details concerning it see page 321. Figures 2A and B are similar diagrams of the median section of the specimen from which figures 25-36 were drawn. The topography shown in these median sections is the basis for the descriptive terms used throughout this text. Except for scattered references to details, the only systematic descriptions of the brain of Amblystoma are in my papers, Bindewald's ('14) on the forebrain, and Larsell's ('20, '32) on the cerebellum. Mention should also be made of Roofe's account ('35) of the endocranial blood vessels and Dempster's paper ('30) on the endolymphatic organ. Kingsbury's admirable paper on Necturus in 1895 may be taken as a point of departure for all further investigation of the brains of urodeles, including my monograph of 1933 and several preceding and following papers. Some of the more important descriptions of the brains of other urodeles are cited in the appended bibliography, notably the following: Salamandra (Kuhlenbeck, '21; Kreht, '30), Proteus (Kreht, '31; Benedetti, '33), Cryptobranchus (Benzon, '26), Gymnophiona (Kuhlenbeck, '22), Siren (Rothig, '11, '24, '27), and several other urodeles in Rothig's later papers, Hynobius, Spelerpes, Diemyctylus (Triturus), Cryptobranchus, Necturus. For the Anura the excellent description of the frog by E. Gaupp in 1899 laid a secure foundation for all subsequent work, and the time is now ripe for a systematic restudy of this brain with the better methods now available and the correlation of the histological structure with physiological experiments specifically designed to reveal the action of this structure. Aronson and Noble ('45) have published an excellent contribution in this field. DEVELOPMENT OF THE BRAIN No comprehensive description of the development of the brain of Amblystoma has been published. The difficulties met in staging specimens by criteria defined by Harrison, Coghill, and others I have discussed elsewhere ('48, chap. x). Griggs ('10) described with [Begin Page: Page 12] 12 THE BRAIN OF THE TIGER SALAMANDER excellent illustrations the early stages of the neural plate and neural tube. Baker ('27) illustrated dorsal and ventral views of the open neural plate, and Baker and Graves ('32) described six models of the brain of A. jeffersonianum from 3 to 17 mm. in length. Burr ('22) described briefly the early development of the cerebral hemispheres. Successive stages of the brain of A. punctatum have been illustrated by Coghill and others (some of which I have cited, '37, p. 391, and '38, p. 208), and at the Wistar Institute there are other models of the brains of physiologically tested specimens. Coghill's papers include a wealth of observation on the development of the mechanisms of the action system, and these were summarized in his London lectures, published in 1929. His reports were supplemented by a series of papers which I published from 1937 to 1941, but these fragmentary observations (of the younger stages particularly) were based on inadequate material and are useful only as preliminary orientation for a more systematic investigation. In Coghill's papers there are accurate projections of all mitotic figures and neuroblasts of the central nervous system in nonmotile, early flexure, coil, and early swimming stages and the arrangement of developing nerve fibers of the brain in the last-mentioned stage (Coghill, '30, Paper IX, fig. 4). On the basis of these data he divided the embryonic brain in front of the isthmus into sixteen regions, each of which is a center of active and characteristic differentiation. These regions are readily identified in our reduced silver preparations of these and later stages. Using a modification of this analysis, I have distinguished and numbered twentytwo such regions in the cerebrum and cerebellum ('37, p. 392), and the development of each of these can be followed through to the adult stage. In my papers of 1937-39 some salient features of these changes are recorded; but this account is incomplete, and more thorough study is urgently needed. In the present work some details only of this development are given in various contexts as listed in the Index under "Embryology." The most detailed description of the development of the urodele brain is the paper by Sumi ('26) on Hynobius. Soderberg ('22) gave a brief description of the development of the forebrain of Triturus (Triton) and a more detailed account of that of the frog, and Rudebeck ('45) has added important observations. The successive changes in the superficial form of the brain can be interpreted only in the light of the internal processes of growth and [Begin Page: Page 13] SALAMANDERS AND THEIR BRAINS 13 differentiation. The need for a comprehensive study of the development of the histological structure of the brain of Amblystoma, including the differentiation of the nervous elements and their fibrous connections, is especially urgent in view of the very large number of experimental studies on developmental mechanics which have been in progress for many years and will probably continue for years to come. Amblystoma has proved to be an especially favorable subject for these studies, and in many of them a satisfactory interpretation of the findings cannot be achieved without more complete knowledge than we now possess of the development of both the nervous tissues and other bodily organs. THE EVOLUTION OF BRAINS The nervous systems of all vertebrates have a common structural plan, which is seen most clearly in early embryonic stages and in the adults of some primitive species. But when the vertebrate phylum is viewed as a whole, the nervous apparatus shows a wider range of adaptive structural modifications of this common plan than is exhibited by any other system of organs of the body. In order to understand the significance of this remarkable plasticity and the processes by which these diverse patterns of nervous organization have been elaborated during the evolutionary history of the vertebrates, it is necessary to find out what were the outstanding features of the nervous system of the primitive ancestral form from which all higher species have been derived. Since the immediate ancestors of the vertebrate phylum have been extinct for millions of years and have left no fossil remains, our only recourse in this search is to examine the most generalized living species, compare them one with another and with embryonic stages, and so discover their common characteristics. This has been done, and we are now able to determine with a high degree of probability the primitive pattern of the vertebrate nervous system. The most generalized living vertebrates (lampreys and hagfish) have brains which most closely resemble that of the hypothetical primordial vertebrate ancestor. The brains of the various groups of fishes show an amazing variety of deviations from the generalized pattern. The paleontological record shows that the first amphibians were derived from one of the less specialized groups of fishes; and there is evidence that the existing salamanders and their allies have preserved until now a type of brain structure which closely resembles [Begin Page: Page 14] 14 THE BRAIN OF THE TIGER SALAMANDER that of the most primitive amphibians and of the generahzed fishes ancestral to them. The internal texture of the brains of the generalized amphibians which are described in this work closely resembles that of the most primitive extant fishes; but the brain as a whole is organized on a higher plane, so that it can more readily be compared with those of reptiles, lower mammals, and man. For this reason the salamanders occupy a strategic position in the phylogenetic series. This examination has brought to light incipient stages of many complicated human structures and some guiding principles of both morphogenesis and physiological action that are instructive. When the first amphibians emerged from the water, they had all the land to themselves ; there were no living enemies there except one another. During aeons of this internecine warfare they carried protective armor; but in later times, during the Age of Reptiles, these more efficient fighters exterminated the clumsy armored amphibians. The more active frogs and toads survived, and so also did the sluggish salamanders and their allies, but only by retiring to concealment in sheltered places. In Devonian times, probably about three hundred million years ago, various species of fishes made excursions to the land and acquired structures adapted for temporary sojourn out of water. Some of the primitive crossopterygian fishes went further and, after a fishlike larval period, experienced a metamorphosis into air-breathing tetrapods. They became amphibians. These were fresh-water species, and the immediate cause of this evolutionary change was extensive continental desiccation during the Devonian period. While their streams and pools were drying up, those fishes which had accessory organs of respiration in addition to the gills of typical fishes, were able to survive and, through further transformations, become airbreathing land animals. An excellent summary of the paleontological evidence upon which the history of the evolution of fishes has been reconstructed has been published by Romer ('46). Two prominent features of this revolutionary change involved the organs of respiration and locomotion, with corresponding changes in the nervous apparatus of control. These systems of organs are typical representatives of the two major subdivisions of all vertebrate bodies and their functions — the visceral and the somatic. The visceral functions and the visceral nervous system will receive scant consideration [Begin Page: Page 15] SALAMANDERS AND THEIR BRAINS 15 in this work, for the material at our disposal is not favorable for the study of these tissues. Here we are concerned primarily with the nervous apparatus of overt behavior, that is, of the somatic adjustments. The most important change in these somatic adjustments during the critical evolutionary period under consideration is the transition from swimming to walking. The fossil record of the transformation of fins into legs is incomplete, but it is adequate to show the salient features of the transformation of crossopterygian fins into amphibian legs (Romer, '46). In the individual development of every salamander and every frog the internal changes in the organization of the nervous system during the transition from swimming to walking can be clearly seen. And these changes are very significant in our present inquiry because they illustrate some general principles of morphogenesis of the brain more clearly than do any other available data. In fishes, swimming is a mass movement requiring the co-ordinated action of most of their muscles in unison, notably the musculature of the trunk and tail. The paired fins are rudders, not organs of propulsion. The young salamander larva has no paired limbs but swims vigorously. This is a typical total pattern of action as defined by Coghill. The adult salamander after metamorphosis may swim in the water like the larva; and he can also walk on land with radically different equipment. Some fishes can crawl out on land, but the modified fins are clumsy and ineflBcient makeshifts compared with the amphibian's mobile legs. Quadrupedal locomotion is a very complicated activity compared with the simple mass movement of swimming. The action of the four appendages and of every segment of each of them must be harmoniously co-ordinated, with accurate timing of the contraction of many small muscles. These local activities are "partial patterns" of behavior, in Coghill's sense. From the physiological standpoint there is great advance, in that the primitive total pattern is supplemented, and in higher animals largely replaced, by a complicated system of co-ordinated partial patterns. This is emphasized here because it provides the key to an understanding of many of the differences between the nervous systems of fishes, salamanders, and mammals. Motility, and particularly locomotion, have played a major role in vertebrate evolution, as dramatically told by Gregory ('43). This outline has been filled in by Howell's ('45) interesting comparative survey of the [Begin Page: Page 16] 16 THE BRAIN OF THE TIGER SALAMANDER mechanisms of locomotion, and I have elsewhere discussed ('48) Coghill's contributions to this theme. In the history of vertebrate evolution there were four critical periods: (1) the emergence of the vertebrate pattern of the nervous system from invertebrate ancestry; (2) the transition from aquatic to terrestrial life; (3) the differentiation within the cerebral hemispheres of primitive cerebral cortex; (4) the culmination of cortical development in mankind, with elaboration of the apparatus requisite for language and other symbolic (semantic) instrumentation of the mental life. 1 . The extinct ancestors of the vertebrates in early Silurian times were probably soft and squashy creatures, not preserved as fossils. Some of their aberrant descendants may be recognized among the Enteropneusta, Tunicata, and Amphioxi ; but the first craniate vertebrates preserved as fossils were highly specialized, heavily armored ostracoderms, now all extinct. 2. The salient features of the second critical period have been mentioned, and here the surviving amphibians recapitulate in ontogeny many instructive features of the ancestral history. 3. Amphibians have no cerebral cortex, that is, superficial laminated gray matter, in the cerebral hemispheres. This first takes definitive form in the reptiles, though prodromal stages of this differentiation can be seen in fishes and amphibians, a theme to which we shall return in chapter vii. 4. The fourth critical period, like the first, does not lie within the scope of this work, though study of the second and third periods brings to light some principles of morphogenesis which may help us to understand the more recondite problems involved in human cortical functions. It is probable that none of the existing Amphibia are primitive in the sense of survival of the original transitional forms and that the urodeles are not only aberrant but in some cases retrograde (Noble, '31; Evans, '44); yet the organization of their nervous systems is generalized along very primitive lines, and these brains seem to me to be more instructive as types ancestral to mammals than any others that might be chosen. They lack the highly divergent specializations seen in most of the fishes; and, in both external form and internal architecture, comparison with the mammalian pattern can be made with more ease and security. So far as structural differentiation has [Begin Page: Page 17] SALAMANDERS AND THEIR BRAINS 17 advanced, it is in directions that point clearly toward the mammalian arrangement. Amphibian eggs and larvae are readily accessible to observation and experiment; they are easily reared; they tolerate experimental operations unusually well; and, in addition, the amphibian neuromuscular system begins to respond to stimulation at a very early age, so that successive stages in maturation of the mechanism are documented by changes in visible overt movement. The adult structure is instructive; and, when the embryological development of this structure is compared with that of higher brains and with the sequence of maturation of patterns of behavior, basic principles of nervous organization are revealed that can be secured in no other way. In the absence of differentiated cerebral cortex, the intrinsic structure of the stem is revealed. Experimental decortication of mammals yields valuable information, but study of such mutilations cannot tell us all that we need to know about the normal operations of the brain stem and the reciprocal relationships between the stem and the cortex. In brief, the brains of urodele amphibians have advanced to a grade of organization typical for all gnathostome vertebrates, Amblystoma being intermediate between the lowest and the highest species of Amphibia. This brain may be used as a pattern or template, that is, as a standard of reference in the study of all other vertebrate brains, both lower and higher in the scale. [Begin Page: Page 18] CHAPTER II THE FORM AND SUBDIVISIONS OF THE BRAIN GROSS STRUCTURE REFERENCE to figures 1-5, 85, and 86 shows that the larger ; subdivisions of the human brain are readily identified in Amblystoma, though with remarkable differences in shape and relative size. When this comparison is carried to further detail, the sculpturing of the ventricular walls shown in the median section is especially instructive. It is again emphasized that the application of mammalian names to the structures here revealed rarely implies exact homology; these areas are to be regarded as primordia from which the designated mammalian structures have been differentiated. The relationships here implied have been established by several independent lines of evidence: (1) The relative positions and fibrous connections of cellular masses and the terminal connections of tracts. In so far as these arrangements conform with the mammalian pattern, they may be regarded as homologous. (2) Embryological evidence. The early neural tubes of amphibians and mammals are similar, and subsequent development of both has been recorded. On the basis of Coghill's observations of rates of proliferation and differentiation in prefunctional stages, the writer ('37) gave arbitrary numbers to recognizable sectors of the neural tube in early functional stages, and the subsequent development of each of these is, in broad lines, similar to that of corresponding mammalian parts. (3) The relationships of svipposed primordia of mammalian structures may be tested by the comparative method. In an arrangement of animal types which approximates the phylogenetic sequence from the most generalized amphibians to man, there are many instances of progressive differentiation of amphibian primordia by successive increments up to the definitive human form. Many pictures of the brains of adult and larval Amblystoma and other urodeles have been published, some of which I have cited ('35a, p. 239). The most accurate pictures of the brain of adult A. tigrinum are those of Roofe ('35), showing dorsal, ventral, and lateral 18 [Begin Page: Page 19] THE FORM AND SUBDIVISIONS OF THE BRAIN 19 aspects and the distribution of endocranial arteries and veins. The outHnes of the brain were drawn from specimens dissected after preservation for 6 weeks in 10 per cent formahn. One of these is shown here (fig. 86 A). Figure IB is drawn from a dissection made by the late Dr. P. S. McKibben, showing the sculpturing of the ventricular surfaces. Figures lA and 85 are drawn from a wax model in which there is some distortion of the natural proportions. Not all the differences seen in these pictures and in the proportions of sections figured are artifact, for the natural variability of urodele brains is surprisingly large (Neimanis, '31). Brains of larval stages have been illustrated by many authors and in my embryological papers of 1937-39. The somewhat simpler brain of the mudpuppy, Necturus, has been described in a series of papers as completely as available material permits, and comparison with the more differentiated structure of Ambly stoma is instructive. The sketches shown in figures 86B and C illustrate the differences between the form of this forebrain and that of Amblystoma. The monograph of 1933 contains a series of diagrams ('33&, figs. 6-16) of the internal connections of the brain of Necturus similar to those of Amblystoma shown here (figs. 7-24). In 1910 I described the general features of the forebrain of A. tigrinum, with a series of drawings of transverse Weigert sections, no. lie, which has subsequently been used as the type specimen. Though this paper contains some errors and some morphological interpretations which I now regard as outmoded ('33a), most of the factual description has stood the test of time, and additional details and reports on other parts of the brain have been published in a series of papers. The most conspicuous external fissures of the brain of Amblystoma are: (1) the longitudinal fissure separating the cerebral hemispheres; (2) the deep stem-hemisphere fissure; (3) a wide dorsal groove separating the epithalamus from the roof (tectum) of the midbrain; (4) the ventral cerebral flexure or plica encephali ventralis, which is a sharp bend of the floor of the midbrain, where it turns downward and backward into the "free part" of the hypothalamus; and (5) the fissura isthmi, extending downward and forward from the anterior medullary velum between midbrain and isthmus. The middle part of the fissura isthmi is at the anterior border of the auricle, which is more prominent in the larva than in the adult ('14a, figs. 1-3). Here in the adult it lies near the posterior border of the internal isthmic tissue, [Begin Page: Page 20] 20 THE BRAIN OF THE TIGER SALAMANDER some distance posteriorly of the ventricular sulcus isthmi; but, like the latter, it really marks the anterior border of the isthmus, as will appear in the description of the development of the isthmic sulcus (p. 179). The obvious superficial eminences on the dorsal aspect of the brain are the small cerebellum, the dorsal convexity of the roof of the midbrain (tectum mesencephali) , the habenular nuclei of the epithalamus, and the two cerebral hemispheres. Posteriorly of the habenulae in the early larvae is the membranous pineal evagination, which in the adult is a closed epithelial vesicle detached from the brain except for the few fibers of the parietal nerve. The lateral aspect of the thalamus, midbrain, and isthmus is a nearly smooth convexity, posteriorly of which is the high auricle, composed of tissue which is transitional between the body of the cerebellum and the acousticolateral area of the medulla oblongata. This auricle contains the primordia of the vestibular part of the cerebellar cortex (flocculonodular lobe of Larsell), and most of its tissue is incorporated within the cerebellum in mammals. On the ventral aspect there is a low eminence in front of the optic chiasma, which marks the position of the very large preoptic nucleus, and a similar eminence behind the chiasma formed by the ventral part of the hypothalamus. The latter is in the position of the human tuber cinereum but is not exactly comparable with it. Most of the hypothalamus is thrust backward under the ventral cerebral flexure as the pars libera hypothalami. The large pars glandularis of the hypophysis envelops the posterior end of the infundibulum and extends spinal ward from it, not anteriorly as in man. The primary subdivisions of the human brain as defined from the embryological studies of Wilhelm His are readily identified in adult Amblystoma, as shown in the median section (fig. 2A). At the anterior end of each cerebral hemisphere is the very large olfactory bulb, the internal structure of which shows some interesting primitive features (p. 54; '246). The bulbar formation extends backward on the lateral side for about half the length of the hemisphere, but on the medial side only as far as the anterior end of the lateral ventricle (figs. 3, 4). Bordering the bulb is an undifferentiated anterior olfactory nucleus, and posteriorly of this the walls of the lateral ventricle show early stages of the differentiation of the major subdivisions of the mammalian hemisphere — in the ventrolateral wall a strio-amygdaloid complex, ventromedially the septum, and dorsally [Begin Page: Page 21] THE FORM AND SUBDIVISIONS OF THE BRAIN 21 the pars pallialis. In the pallial part no laminated cortical gray is differentiated, but there are well-defined pallial fields: dorsomedially, the primordial hippocampus; dorsolaterally, the primordial piriform lobe; and between these a primordium pallii dorsalis of uncertain relationships. The boundaries of the diencephalon, as here defined and shown in figure 2A, are: anteriorly, the stem-hemisphere fissure and the posterior border of the anterior commissure ridge and, posteriorly, the anterior face of the posterior commissure and the underlying commissural eminence and, more ventrally, the sulcus, s, which marks the anterior border of the cerebral peduncle. The inclusion of the preoptic nucleus is in controversy; but, whether or not this inclusion is justifiable morphologically, its relationships with the hypothalamus are so intimate that it is practically convenient to consider these parts together. The four primary subdivisions of the diencephalon as I defined them in 1910 are: (1) the dorsal epithalamus, containing on each side the habenula and pars intercalaris, the latter including the pretectal nucleus; (2) pars dorsalis thalami, which is the primordium of the sensory nuclei of the mammalian thalamus; (3) pars ventralis thalami, the motor zone of the thalamus, or subthalamus; (4) hypothalamus. The mammalian homologies of these areas are clear, though their relative sizes and fibrous connections exhibit remarkable differences. The posterior boundary of the mesencephalon is marked by the external fissura isthmi, the ventricular sulcus isthmi (fig. 2B, s.is.), and ventrally in the floor plate a pit, the fovea isthmi [f.i.). These are all more prominent in the larva than in the adult. This sector includes the posterior commissure, the tectum mesencephali (primordial corpora quadrigemina) , the underlying dorsal tegmentum (subtectal area), and the area surrounding the tuberculum posterius at the ventral cerebral flexure, termed the "nucleus of the tuberculum posterius." On embryological grounds and for convenience of description, this ventral area, which is bounded by the variable ventricular sulcus s, is here called the "peduncle" in a restricted sense ('36, p. 298; '396, p. 582). This is a primordial mesencephalic structure which is not the equivalent of the peduncle of human neurology. Amblystoma has nothing comparable with the human basis pedunculi, and its "peduncle" is incorporated within the tegmentum of the human brain. The III cranial nerve arises within the "peduncle" and emerges near the fovea isthmi. The nucleus of the IV nerve is in the [Begin Page: Page 22] 2^2 THE BRAIN OF THE TIGER SALAMANDER isthmus. In the human brain there are no definite structures comparable to the amphibian dorsal and isthmic tegmentum. The isthmus is much more clearly defined than in adult higher brains, it is relatively larger, and its physiological importance is correspondingly greater, as will appear later. It is bounded anteriorly by the sharp isthmic sulcus and posteriorly by the cerebellum, auricle, and trigeminal tegmentum. The so-called "pons" sector of the human brain stem is named from its most conspicuous component, but this name is meaningless in comparative anatomy. In man it is the pons and the sector of the stem embraced by it; but in no two species of mammals is the part embraced by the pons equivalent; and below the mammals the pons disappears entirely. The medulla oblongata, on the other hand, is a stable structure, extending from the isthmus to the spinal cord, and for it the shorter name "bulb" is sometimes used, especially in compounds. I outlined the development and morphological significance of the urodele cerebellum ('14, '24), and this was followed by detailed descriptions of the development and adult structure of this region of Amblystoma by Larsell ('20, '32), whose observations I have subsequently confirmed, including his fundamental distinction between its general and its vestibular components. Some features of the larval medulla oblongata and related nerves have been described ('14a, '396) and, more recently ('446), additional details of the adult, particularly the structures at the bulbospinal junction. Much remains to be done to clarify the organization of the medulla oblongata and spinal cord. The cranial nerves and their analysis into functional components (chap, v) were described by Coghill ('02). The embryological development of these components also has been extensively studied (chap. x). The arrangement and composition of these nerves are fundamentally similar to those of man, with a few notable exceptions. The internal ear lacks the cochlea, which is represented by a very primitive rudiment; a cochlear nerve, accordingly, is not separately differentiated. There is an elaborate system of cutaneous organs of the lateral lines, whose functions are not as yet adequately known. These are supplied by very large nerves commonly assigned to the VII and X pairs, though it would be more appropriate to regard them as accessory VIII nerves, for all these nerve roots enter a wide zone at the dorsolateral margin of the medulla oblongata known as the "area acusticolateralis." There is no separate XI cranial nerve, this being [Begin Page: Page 23] THE FORM AND SUBDIVISIONS OF THE BRAIN 23 represented by an accessorius branch of the vagus. The XII nerve is represented by branches of the first and second spinal nerves. The first spinal nerve in some specimens has a small ganglion ; the second nerve always has a large dorsal root and ganglion. In this connection a passage in the comprehensive work on the anatomy of Salamandra by Francis ('34, p. 134) is worthy of mention: "After making due allowance for the absence of a lateralis component in the adult salamander, the correspondence between the cranial nerves of this animal and those of Ambly stoma is very close indeed." The configuration and mutual relations of the gross structures just surveyed can be seen only in sections, of which many, cut in various planes, have been illustrated in the literature. Only a few selected examples are included in the present work, with references in subsequent chapters to many others. For general orientation the following figures may be consulted : a series of selected transverse sections from the spinal cord to the olfactory bulb (figs. 87-100); a series of horizontal sections through the middle part of the brain stem (figs. 25-36); a few sagittal sections (figs. 101-4). Figures 6-24 show the chief fibrous connections of each well-defined region of the brain stem. The diencephalon, mesencephalon, and isthmus have the form of three irregular pyramids oppositely oriented (fig. 2A). The broad base of the diencephalon extends from the anterior commissure to the hypophysis, and the apex is at the epiphysis. The tectum forms the base of the mesencephalic pyramid, and the apex is at the ventral tip of the tuberculum posterius, which borders the ventral cerebral flexure. The base of the pyramidal isthmus is formed by the massive tegmentum isthmi of each side and the median interpeduncular nucleus in the floor plate. It narrows dorsally into the anterior medullary velum between the tectum and the cerebellum. The middle sectors of the brain stem — diencephalon, mesencephalon, and isthmus — contain the primordial regulatory and integrating apparatus controlling the fundamental sensori-motor systems of adjustment. The most important peripheral connections are with the eyes, and these in most vertebrates play the dominant role in maintaining successful adjustment with environment. From this topographical feature it naturally followed that, during the course of phylogenetic differentiation of the brain, the chief centers of adjustment of the other exteroceptive systems were elaborated in close juxtaposition with the visual field in the midbrain and thalamus. ^{LIBRARY v^ [Begin Page: Page 24] 24 THE BRAIN OF THE TIGER SALAMANDER Here they are interpolated between the primary sensory and motor apparatus of the medulla oblongata and spinal cord below and the great olfactory field and suprasegmental apparatus of the cerebral hemispheres above. In all lower vertebrates the roof of the midbrain, the tectum, is the supreme center of regulation of motor responses to the exteroceptive systems of sense organs. The hypothalamus is similarly elaborated for regulation of olfacto- visceral adjustments. The patterning of motor responses for both these groups of receptors is effected in the cerebral peduncle and tegmentum. In the region of the isthmus, between the tectum and the primary vestibular area of the medulla oblongata and above the tegmentum, the cerebellum was elaborated as the supreme adjustor of all proprioceptive systems. At the rostral end of the brain, within and above the specific olfactory area of the cerebral hemisphere, there gradually emerged a synthetic apparatus of control, adapted to integrate the activities of all the other parts of the nervous system and to enlarge capacity to modify performance as a result of individual experience. In the lowest vertebrates this "suprasensory" and "supra-associational" apparatus, as Coghill termed it, is not concentrated in the cerebral hemispheres, but it is dispersed, chiefly in the form of diflfuse neuropil. In the amphibian cerebral hemispheres this integrating apparatus is more highly elaborated than elsewhere, with some local differentiation of structure. The hemispheres are larger than in fishes, and the primordia of their chief mammalian subdivisions can be recognized. A dorsal pallial part is distinguishable from a basal or stem part of the hemisphere, though the distinctive characteristics of the pallium are only incipient. There is no cerebral cortex, and, accordingly, the mammalian cortical dependencies in the thalamus, midbrain, and cerebellum have not yet appeared. The primordial thalamus is concerned chiefly with adjustments within the brain stem, though precursors of the thalamic radiations to the hemispheres are present. VENTRICLES The lateral ventricles of the cerebral hemispheres have the typical form except at the interventricular foramen, where the amphibian arrangement is peculiar. The anterior and hippocampal commissures do not cross as usual in or above the lamina terminalis, but in a more posterior high commissural ridge ; and between these structures there is a wide precommissural recess, into which the interventricular [Begin Page: Page 25] THE FORM AND SUBDIVISIONS OF THE BRAIN 25 foramina open. This results in some radical differences from reptilian and mammalian arrangements of the related fiber tracts and membranous parts, as elsewhere described (p. 291; '35). The third ventricle is expanded dorsally into the complicated membranous paraphysis and dorsal sac. Ventrally, the great elongation of the preoptic nucleus gives rise to a large preoptic recess between the anterior commissure ridge and the chiasma ridge, and in front of the latter there is a lateral optic recess (fig. 96), which in early larval stages extends outward as far as the eyeball, as a patent lumen of the optic nerve ('41), an arrangement which persists in the intracranial part of the nerve of adult Necturus ('41a). In the hypothalamus the ventricle is dilated laterally ('35a, p. 253; '36, figs. 10-14), and posteriorly it is a wide infundibulum with membranous roof and thin but nervous floor and posterior wall. The latter is the pars nervosa of the hypophysis and is partly enveloped by the pars glandularis (figs. 2, 101; '35a, p. 254; '42, p. 212 and figs. 56-65; Roofe, '37). The aqueduct of the midbrain is greatly expanded dorsoventrally. Its ventral part is contracted laterally by the thick peduncles and tegmentum, and the dorsal part is dilated as an optocoele. The sulcus lateralis mesencephali marks its widest extent, and tectal structure reaches far below this sulcus. The fourth ventricle is of typical form except anteriorly, where the wide lateral recess with membranous roof extends outward and forward to cover the whole dorsolateral aspect of the auricular lobe (figs. 90, 91 ; '24, p. 627). The rhombencephalic chorioid plexus is elaborately developed in interesting relation with the peculiar endolymphatic organs of this animal ('35, p. 310). The ventricular systems of adult Triturus (Diemyctylus) and of larval and adult stages of Hynobius have been described and illustrated with wax models bySumi('26, '26a). The ventricular surface of both larvae and adults is clothed with very long cilia. These are not preserved in ordinary preparations and in our material are seen only in Golgi sections, where their impregnation is erratic and local ('42, p. 196). They are most frequently seen in the infundibulum and optocoele under the tectum. In the vicinity of the posterior commissure the ciliated ependyma is thickened (subcommissural organ of Dendy), and to it the fiber of Reissner is attached ('42, p. 197). This thick, nonnervous fiber extends backward through the ventricle to the lower end of the spinal cord and, like the cilia, is apparently an outgrowth from the internal ependymal membrane. [Begin Page: Page 26] 26 THE BRAIN OF THE TIGER SALAMANDER MENINGES, CHORIOID PLEXUSES, AND BLOOD VESSELS The meninges of Amblystoma were described in 1935. This account shoukl be compared with that of Salamandra pubhshed in 1934 by Francis, whose description was based on the investigation of Miss Helen O'NeiU ('98), done under the direction of Wiedersheim and Gaupp. In Amblystoma the meninges are intermediate between the meninx primitiva of the lower fishes and those of the frog. Over the spinal cord and most parts of the brain a firm and well-defined pachymeninx, or dura, closely invests the underlying undifferentiated pia-arachnoid. The meninges of the frog have been described by others, and recently Palay ('44) has investigated their histological structure in the toad. The most interesting feature of these amphibian membranes is their intimate relation with the enormous endolymphatic organ described by Dempster ('30) and the associated blood vessels. The vascular supply of these brains is peculiar in several respects. The distribution of arteries and veins has been described by Roofe ('35, '38), and I have added some details from the adult ('35) and the larva {'Md). The endocranial veins form a double portal system of sinusoids of vast extent and unknown significance. Between the cerebral hemispheres and the epithalamus the nodus vasculosus (Gaupp) is permeated by a complicated rete of sinusoids, which receives venous blood from the entire prosencephalon— chorioid plexuses, brain wall, and meninges. The efferent discharge from this rete is by the two oblique sinuses, which pass backward across the midbrain to enter a similar rete of wide, anastomosing smusoids spread over the chorioid plexus of the fourth ventricle and the lobules of the endolymphatic organs. This rete also receives the vems from all posterior parts of the brain, meninges, and chorioid plexus. The common discharge for all this endocranial venous blood is by a large sinus, which emerges from the cranium through the jugular foramen and joins the jugular vein. These membranous structures are readily observable in the living animal without serious disturbance of normal conditions, and they provide unique opportunities or experimental study of some fundamental problems of vascular ^\\' wSomted out by Craigie ('38, '38a, '39, '45) that within the substance of this brain the penetrating blood vessels are arranged in two ways-a capillary net of usual type and simple loops, which [Begin Page: Page 27] THE FORM AND SUBDIVISIONS OF THE BRAIN 27 enter from the meningeal arterial network. Our preparations confirm this observation and also the fact that the vascular pattern varies in different parts of the brain. Both isolated loops and the capillary net may be seen in the same field, as in the dorsal thalamus (fig. 44), or one of these patterns may prevail, with few, if any, instances of the other. In the tectum and dorsal tegmentum of the midbrain, for instance, the tissue is vascularized by simple loops with only occasional anastomosis (fig. 48), while in the underlying peduncle and isthmic tegmentum the vascular network prevails, with occasional simple loops. In the meninges and chorioid plexuses only the network has been observed. The telencephalic and diencephalic chorioid plexuses have an abundant arterial blood supply through the medial hemispheral artery; but the elaborately ramified tubules of the paraphysis seem to have no arterial supply or capillary net, the accompanying vessels being exclusively venous sinusoids ('35, p. 342). The same seems to be true of the endolymphatic sacs ('34c?, p. 543). The chorioid plexus of the fourth ventricle has abundant arterial blood supply. In all plexuses the capillaries unite into venules, which discharge into wide sinusoids, which ramify throughout the plexus and have very thin walls. All arterioles of the chorioid plexuses are richly innervated, but it has not been possible to get satisfactory evidence of the sources of these nerve fibers ('36, p. 343; '42, p. 255; Necturus, '336, p. 15). The enormous development of the chorioid plexuses and associated endolymphatic organ of urodeles is apparently correlated with the sluggish mode of life and relatively poor provision for aeration of the blood. In the more active anurans the plexuses are smaller; but in the sluggish mudfishes, including the lungfishes, with habits similar to those of urodeles, we again find exaggerated development of these plexuses. Existing species in the border zone between aquatic and aerial respiration are all slow-moving and relatively inactive. The enlarged plexuses and sinusoids give vastly increased surfaces for passage of blood gases into the cerebrospinal fluid; and, correlated with this, the brain wall is thin everywhere, to facilitate transfer of metabolites between brain tissue and cerebrospinal fluid. Massive thickenings of the brain wall occur in many fishes and in amniote vertebrates, but not in mudfishes and urodeles. [Begin Page: Page 28] CHAPTER III HISTOLOGICAL STRUCTURE GENERAL HISTOLOGY IN AMPHIBIAN brains the histological texture is generalized, exhibiting some embryonic features; and it is at so primitive a level of organization as to make comparison with mammals difficult. Most of the nerve cells are small, with scanty and relatively undifferentiated cytoplasm. There are some notable exceptions, such as the two giant Mauthner's cells of the medulla oblongata and related elements of the nucleus motorius tegmenti. With the exceptions just noted, Nissl bodies are absent or small and dispersed. Almost all bodies of the neurons are crowded close to the ventricle in a dense central gray layer, with thick dendrites directed outward to arborize in the overlying white substance (figs. 9, 99). The axon usually arises from the base of the dendritic arborization, rarely from its tip, and sometimes from the cell body; it may be short and much branched or very long, with or without collateral branches. The ramifications of the short axons and of collaterals and terminals of the longer fibers interweave with dendritic arborizations to form a more or less dense neuropil, which permeates the entire substance of the brain and is a synaptic field. Some of the nerve fibers are myelinated, more in the peripheral nerves, spinal cord, and medulla oblongata than in higher levels of the brain. Both myelinated and unmyelinated fibers may be assembled in definite tracts, or they may be so dispersed in the neuropil as to make analysis difficult. The arrangement of recognizable tracts conforms with that of higher brains, so that homologies with human tracts are in most cases clear. These tracts and the gray areas with which they are connected provide the most useful landmarks in the analysis of this enigmatic tissue. In the gray substance there are few sharply defined nuclei like those of mammals, but the precursors of many of these can be recognized as local specializations of the elements or by the connections of the related nerve fibers. In most cases the cells of these primordial nuclei have long dendrites, which arborize widely into surrounding fields (figs. 9, 24, 61, 66), so that the functional specificity of the [Begin Page: Page 29] HISTOLOGICAL STRUCTURE 29 nucleus is, at best, incomplete. This arrangement facilitates mass movements of "total-pattern" type, but local differentiations serving "partial patterns" of action (Coghill) are incipient. Localized reflex arcs are recognizable, though in most cases these are pathways of preferential discharge within a more dispersed system of conductors (chap. vi). Tissue differentiation is more advanced in the white substance than in the gray. The most important and diversely specialized synaptic fields are in the alba, and this local specialization is correlated with differences in the physiological properties of the nervous elements represented. This means, as I see it, that functional factors must be taken into account in both ontogenetic and phylogenetic differentiation and that in the long view the problems of morphogenesis are essentially physiological, that is, they resolve into questions of adaptation of organism to environment (chap. viii). This is the reason why in this work the histological analysis is made in terms of physiological criteria, even though these criteria are, in the main, based on indirect evidence, namely, the linkage of structures in functional systems of conductors. The nonnervous components of this tissue comprise the blood vessels, ependyma, and a small number of cells of uncertain relationships which are regarded as undifferentiated free glial cells or transitional elements ('34, p. 94; '336, p. 17). The ependymal elements everywhere span the entire thickness of the brain wall with much free arborization. They assume various forms in different regions, and their arrangement suggests that they are not merely passive supporting structures, though if they have other specific functions these are still to be discovered. For illustrations see figures 63, 64, 70, 79, and 81. More detailed descriptions of the histological structure of urodele brains may be found in earlier papers ('14a, p. 381; '17, pp. 232, 279 ff.; '335, pp. 16, 268; '33c; '33cf; '34; '34a,- '346; '42, p. 195; '44a). In the olfactory bulbs of Necturus ('31) and Amblystoma ('246) we find an interesting series of transitional cells between apparently primitive nonpolarized elements and typical neurons, as described on page 54. THE NEUROPIL In the generalized brains here under consideration the neuropil is so abundant and so widely spread that it evidently plays a major role in all central adjustments, thus meriting detailed description. [Begin Page: Page 30] 30 THE BRAIN OF THE TIGER SALAMANDER Only the coarser features of this tissue are open to inspection with presently available histological technique. In my experience its texture is best revealed by Golgi preparations, and very many of them, for the erratic incidence of these impregnations may select in different specimens now one, now another, of the component tissues — blood vessels, ependyma, dendrites, or axons. In each area of neuropil these components are independent variables, and in most of these areas axons from many sources are so intricately interwoven that the tissue can be resolved only where fortunate elective impregnations pick out one or another of the several systems of fibers in different specimens. It is difficult to picture the neuropil either photographically or with the pen, and the crude drawings in this book and in the literature give inadequate representations of the intricacy and delicacy of its texture. A survey of the neuropil of adult Amblystoma as a whole has led me to subdivide it for descriptive purposes and somewhat arbitrarily into four layers ('42, p. 202). From within outward, these are as follows: 1. The periventricular neuropil pervades the central gray so that every cell body is enmeshed within a fabric of interwoven slender axons (figs. 106, 107). This persists in some parts of the mammalian brain as subependymal and periventricular systems of fibers. 2. The deep neuropil of the alba at the boundary between gray and white substance knits the periventricular and intermediate neuropil together, and it also contains many long fibers coursing parallel with the surface of the gray. The latter are chiefly efferent fibers directed toward lower motor fields (fig. 93, layer 5; '42, figs. 18-21, 24, 29-45, 47). 3. The intermediate neuropil in the middle depth of the alba contains the largest and most complicated fields of this tissue. It is very unevenly developed, in some places scarcely recognizable and in others of wide extent and thickness. Its characteristics are especially well seen in the corpus striatum (figs. 98, 99, 108, 109), thalamus ('396, fig. 81; '42, figs. 71, 81), and tectum opticum (figs. 93, layer 2, 101; '42, figs. 26, 30, 32, 79-83). Many of the long tracts lie within this layer and have been differentiated from it. Most of the specific nuclei of higher animals, including the outer gray layers of the tectum, have been formed by migration of neuroblasts from the central gray outward into this layer. Here we find much of the ap[ Begin Page: Page 31] HISTOLOGICAL STRUCTURE 31 paratus of local reflexes and their organization into the larger, innate patterns of behavior. 4. The superficial neuropil is a subpial sheet of dendritic and axonal terminals, in some places absent, in others very elaborately organized. Here are some of the most highly specialized mechanisms of correlation in the amphibian brain, from which specific nuclei of higher brains have been developed. Notable examples are seen in the interpeduncular neuropil (chap, xiv) and the ventrolateral neuropil of the cerebral peduncle described in the next section. This neuropil seems to be a more sensitive medium for strictly individual adjustments (conditioning) than the deeper neuropil, but of this there is no experimental evidence. This hypothesis is supported by the fact that in higher animals cerebral cortex develops within this layer and apparently by neurobiotactic influence emanating from it. In the first synapses observed in embryogenesis numerous axonic terminals converge to activate a single final common path (Coghill, '29, p. 13), This is the first step in the elaboration of neuropil. As differentiation advances, neurons are segregated to serve the several modalities of sense and the several systems of synergic muscles, and these systems are interconnected by central correlating elements. In no case are these connections made by an isolated «hain of neurons in one-to-one contact between receptor and effector. The central terminals of afferent fibers from different sense organs are widely spread and intermingled. Dendrites of the correlating cells branch widely in this common receptive field, and the axons of some of them again branch widely in a motor field, thus activating neurons of the several motor systems. This arrangement is perfectly adapted to evoke mass movement of the entire musculature from any kind of sensory stimulation, and this is, indeed, the only activity observed in early embryonic stages. It is the rare exception rather than the rule for a peripheral sensory fiber to effect functional connection directly with a peripheral motor neuron. One or more correlating elements are interpolated; and, as differentiation advances, the number of these correlating neurons is enormously increased in both sensory and motor zones and also in the intervening intermediate zone. The axons of these intrinsic elements ramify widely in all directions, and, as a rule, they or collaterals from them interweave to form the closely knit fabric which pervades both gray and white substance everywhere. This is the [Begin Page: Page 32] 32 THE BRAIN OF THE TIGER SALAMANDER axonic neuropil, within the meshes of which dendrites of neurons ramify widely. These axons are unmyelinated, and every contact with a dendrite or a cell body is a synaptic junction. Eveiy axon contacts many dendrites, and every dendrite has contact with many axons, and these may come from near or from very remote parts. All neuropil is a synaptic field, and, since in these amphibian brains it is an almost continuous fabric spread throughout the bram, its action is fundamentally integrative. But it is more than this. It is germinative tissue, the matrix from which much specialized structure of higher brains has been differentiated. It is activated locally or diffusely by every nervous impulse that passes through the substance of the brain, and these impulses may irradiate for longer or shorter distances in directions determined by the trend of the nerve fibers of which it is composed. This web of conductors is relatively undifferentiated, but it is by no means homogeneous or equipotential, for each area of neuropil has characteristic structure and its own pattern of peripheral and central connections. Many of these fibers, which take long courses, may connect particular areas of gray substance either in dispersed arrangement or assembled as recognizable tracts. In fact, we find all gradations between an almost homogeneous web of neuropil and long well-fasciculated tracts of unmyelinated or myelinated fibers. Many of these long fibers have collateral connections throughout their length; others are well-insulated conductors between origin and termination. The web of neuropil shows remarkable diversity in different regions. In some places it is greatly reduced, as, for instance, in the ventral funiculi, where the alba is densely filled with myelinated fibers; in other places there are local concentrations of dendrites and finest axons so dense that in ordinary haematoxylin or carmine preparations they appear as darker fields, the Punksuhstanz of the early histologists and the glomeruli of the olfactory bulb and interpeduncular nucleus (chap. xiv). When some of these fields are analyzed, it is found that their fibrous connections conform with those of specific "nuclei" of higher brains. In Ambly stoma such a field is not a "nucleus," for it contains no cell bodies; but examination of the corresponding area in anurans and reptiles may show all stages in the differentiation of a true nucleus by migration of cell bodies from the central gray outward into the alba ('27, p. 232). Such a series of phylogenetic changes can be readily followed in the corpus striatum, the geniculate bodies, the interpeduncular nucleus, and many other [Begin Page: Page 33] HISTOLOGICAL STRUCTURE 33 places and particularly in the tectum opticum and the pallial fields of the cerebral hemispheres. In phylogeny the long, well-organized tracts seem to have been formed by a concentration of the fibers of the neuropil. The diffuse neuropil is probably the primordial form, going back to the earliest evolutionary stages of nervous differentiation (coelenterates) . Local reflex arcs and specific associational tracts have been gradually differentiated within it, that is, integration precedes local specialization, the total pattern antedates the partial patterns. In ontogeny, especially of higher animals, this history may not be recapitulated, and tracts serving local reflexes may appear very early; but in Amblystoma, even in the adult stage, there are few tracts which are compactly fasciculated and free from functional connection with the surrounding neuropil. Most of the long, well-fasciculated tracts have some myelinated fibers that seem to have functional connections only at their ends; but these are accompanied by others, which are without myelin and are provided with numberless collaterals tied into the enveloping neuropil. There is, accordingly, a seepage of nervous influence along the entire length of these tracts. From the primordial diffuse neuropil, differentiation advanced in two divergent directions. One of these, as just pointed out, led to the elaboration of the stable architectural framework of nuclei and tracts, the description of which comprises the larger part of current neuroanatomy. This IS the heritable structure, which determines the basic patterns of those components of behavior which are common to all members of the species. The second derivative of the primordial neuropil is the apparatus of individually modifiable behavior — conditioning, learning, and ultimately the highly specialized associational tissues of the cerebral cortex. In both phylogeny and ontogeny, differentiation of the first type precedes that of the second. Primitive animals and younger developmental stages exhibit more stable and predictable patterns of behavior; and the more labile patterns are acquired later. In Amblystoma both these types of differentiation are at low levels, but they are sufficiently advanced to be clearly recognizable. Tissue differentiation is further advanced in the white substance than in the underlying gray. During the course of this progressive specialization of tissue, the primordial integrative function of the neuropil is preserved and elaborated. The mechanism employed is seen in its most generalized form in the deep periventricular neuropil, layer 1 of the preceding [Begin Page: Page 34] 34 THE BRAIN OF THE TIGER SALAMANDER analysis. This is a close-meshed web of finest axons, within which all cell bodies are imbedded. It is everywhere present, providing continuous activation (or potential activation) of every neuron, summation, reinforcement, or inhibition of whatever activities may be going on in the more superficial layers and affecting the general excitatory state of the whole central nervous system. It receives fibers from all sensory and motor fields and seems to be the basic apparatus of integration. In man this type of tissue survives in the periventricular gray of the diencephalon, and, as suggested by Wallenberg ('31), it probably plays an important part in determining the disposition and temperament of the individual ('34rt, pp. 241, 245). This unspecialized tissue may serve the most general totalizing function. From it there have been derived the complicated mechanisms for synthesizing the separate experiences and organizing them in adaptive patterns — a process of differentiation which culminates in the human cerebral cortex. The relations of neuropil to reflex arcs are discussed in chapter vi. The relative abundance of myelinated fibers is a rough indicator of the relation between stable and labile types of performance. Thus the myelinated white substance is relatively greater in the spinal cord than in the brain, and the ratio of myelinated to unmyelinated tissue diminishes as we pass forward in the brain, as is well illustrated by a published series of Weigert sections drawn from a single specimen (no. IIC) from the olfactory bulb to the spinal cord ('10, figs. 8-21; '25, figs. 2-9; '44&, figs. 1-6). This is because the myelinated fibers, most of which are long conductors of through traffic, tend to be compactly arranged, with relatively scanty collateral connections with the neuropil. In the gray substance there is a similar increment m relative amount of neuropil as we pass forward from spinal cord to hemispheres, the higher levels being specialized for correlation, association, conditioning, and integration and the lower levels for stabilized total activities and reflexes. In the phylogenetic series this principle takes a form which can be quantitatively expressed as Economo's coefiicient of the ratio between total gray substance and the mass of the nerve cells contained within it. The lower the animal species in the scale, the greater is the mass of the cells compared with the gray substance. This law may be expressed in the converse form: Higher animals have a larger proportion of neuropil in the gray substance, thus giving them capacity for conditioning and other individually [Begin Page: Page 35] HISTOLOGICAL STRUCTURE 3r> acquired patterns of behavior (Economo, '26, '29). No mathematical precision should be claimed for these laws, but they do express the general trend of our experience. For additional data and critical comment see von Bonin on page 64 of the monograph by Bucy and others ('44). The properties of amphibian neuropil have been discussed in several places, in addition to the summary already cited ('42, p. 199). In one of these papers ('33c?) the geniculate neuropil of Necturus was described, and later ('42, p. 280) the quite different arrangement of Anibly stoma (compare the corresponding structure of the frog, '25), together with a full account of the neuropil of the optic tectum and its connections (here, again, comparison with the more differentiated structure of the frog is instructive). In connection with a general survey of the neuropil of Necturus, its peculiar relations in the pallial part of the hemisphere were discussed in four papers ('336, p. 176; '336?, '34, '34a). Amblystoma is similar ('27), though the details have not been fully explored. In the pallial field the four layers of neuropil tend to merge into a single apparatus of association. This is corticogenetic tissue within which the earliest phases of incipient differentiation of laminated cortex can be recognized in the hippocampal area, as described in chapter vii. Some samples of the appearance of elective Golgi impregnations of amphibian neuropil are shown in the accompanying illustrations, and many others are in the literature. The related morphological and physiological problems can best be presented in the form of illustrative examples, one of which is the striatal neuropil (chap, vii), another the interpeduncular neuropil described in chapter xiv, and still another in the superficial ventrolateral neuropil of the peduncle, the area ventrolateralis pedunculi, which will next be described. THE VENTROLATERAL PEDUNCULAR NEUROPIL The "peduncle" in the restricted sense as here defined, together with the adjoining tegmentum, is the chief central motor pool of the skeletal muscles. Efferent fibers from it are among the first to appear in the upper brain stem in embryogenesis, descending in the primary motor path, which is the precursor of the fasciculus longitudinalis medialis, and activating the musculature of the trunk. A second efferent path, which appears very early, goes out directly to the periphery through the oculomotor nerve. The first sensory influence to act upon this pool comes from the optic tectum through the posterior commissure in the S-reaction stage. In subsequent stages it is entered by fibers from many other sources, including the basal optic tract (fig. 14) and the olfacto-peduncular and strio-peduncular tracts (fig. 6). In the adult animal, motor impulses issuing from this pool are probably concerned [Begin Page: Page 36] 36 THE BRAIN OF THE TIGER SALAMANDER primarily with synergic activation of large masses of muscle, notably those concerned with locomotion and conjugate movements of the eyes. Control of the movements directly involved in seizing and swallowing food is believed to be chiefly in the isthmic tegmentum, and this apparatus matures later n ontogeny. The chief synaptic connections of the great motor pool of the peduncle are in the intermediate, deep, and periventricular layers of neuropil. External to these is a ventrolateral band of dense neuropil extending from the root of the III nerve forward along the entire length of the peduncle. In former papers this has been termed "area lateralis tegmenti" and "nucleus ectomamillaris," but both these names now seem to me inappropriate ('4'-2, p. 233). This band receives at the anterior end all the terminals of the large basal optic tract (figs. U, 94) and, at the posterior end, terminals of the secondary and tertiary ascending ^'isceral sensory and gustatory tracts (figs. 8, 23). The terminals of these two systems of fibers are intimately interlaced, and among them are dendritic arborizations of tlie underlying cells of the peduncle into which optic, olfactory, and visceral systems of nervous impulses converge and through which the combined effect is transmitted in the outgoing motor pathways. These seem to be the primary components of this neuropil, and to them are added axonic terminals from a wide variety of sources, the most notal)le of which are sketched in figure '23 (compare Necturus, '34, p. 103 and fig. 4). The peduncular dendrites, which arborize within this neuropil, include some from the nucleus of the oculomotor nerve (fig. 24; '42, p. 275), so that here fibers of the basal optic tract coming directly from the retina may synapse with peripheral motor neurons — one of the rare examples of a two-neuron arc witli only one synapse between the peripheral receptor and the effector, though even here there are at least two additional synapses in this arc within the retina. Other peduncular neurons may transmit retinal excitations downward through the ventral tegmental fascicles to all lower motor fields. At its anterior end this neuropil is connected by fibers conducting in both directions with the dorsal (mamillary) part of tlie hypothalamus, as in Necturus ('346, fig. 3), and also with its ventral (infundibular) part (fig. 23; "42, pp. 226, 227). This is an extension of the visceral-gustatory tract into the hypothalamus, and it may be that some of the visceral fibers pass without interruption through the peduncular neuropil to the hypothalamus, though this has not been satisfactorily demonstrated. In some fishes such a direct connection is evident and large; in mammals the course of the ascending visceral-gustatory path is still uncertain. Other connections of this neuropil, as shown in figure 23, include terminals of the olfacto-peduncular tract from the anterior olfactory nucleus, probably the nervus terminalis (observed in Necturus) fibers from the tectum, pretectal nucleus, dorsal and ventral thalamus, and terminals of the fasciculus retroflexus (p. 202 and fig. 20). These terminals of fibers from surprisingly diverse sources are all closely interwoven with one anotlier and with the terminal dendrites of peduncular neurons, a unique arrangement occurring, so far as known, only in Amphibia. I have indulged in the following speculations upon its possible physiological significance. In the first place, it is clear that this curious tissue is either an undifferentiated primordium of a number of structures which are separately differentiated in more specialized brains, or else it is a retrograde fusion of several such structures. The former supposition seems more probable, for the phylogenetic history of one of its components is easily read ('25, pp. 443-49). In Necturus there are no cell bodies directly associated with this neuropil; in Amblystoma a few cells have migrated out of the gray layer to its border (fig. 24) ; and in the frog the optic component of the neuropil is separate and surrounded by a spherical shell of cell bodies, which is a true basal optic nucleus (Gaupp, '99, p. 54, fig. 19). This nucleus attains large size and [Begin Page: Page 37] HISTOLOGICAL STRUCTURE 37 complexity in some reptiles, as described by Slianklin ('3.'3) and others. In the mammals it retains its individuality as the chief terminus of basal optic fibers, though other fibers of this system are rather widely spreatl in the surrounding tegmentum (Gillilan, '41). The history of the visceral and other components of the amphibian ventrolateral neuropil has not yet been written. In my recent description ('42) of the optic system of Amblystoma, special attention was given to the central distribution of thick and thin fibers from the retina, and this was followed ('42, p. 295) by some speculations about its physiological significance. In development the thick fibers appear first, and the number of thin fibers is enormously increased in later stages, particularly at the time of metamorphosis. Thick fibers conduct more rapidly than thin fibers, and this time factor may play an important part in the central analysis of mixed retinal excitation. Both thick and thin fibers end in the thalamus, pretectal nucleus, and tectum; and in each of these fields their terminals are mingled, not segregated. The optic fibers to the basal peduncular neuropil are moderately thick; upon retinal stimulation this field, accordingly, is the first to be activated, and its excitation of the underlying peduncular neurons may precede any influence upon these cells from the longer paths by way of the tectum and thalamus. Figure 22 shows in continuous lines the major optic tracts and the motor paths from the peduncle, and in broken lines some internuncial connections. The thick fibers which descend from the tectum and thalamus are myelinated; some of them are crossed in the posterior commissure and the commissure of the tuberculum posterius, and some are uncrossed. They connect primarily with the descending pathway in the ventral tegmental fascicles (f.r.t.). The thinner correlating fibers take other pathways, and they may make synaptic connection with peduncular neurons in any one or all of the four layers of the neuropil. The efl'erent path may be to low er motor centers through the ventral tegmental fascicles or to the muscles of the eyeball through the III nerve. Figures 24 and 93 are diagrammatic transverse sections at the level of the III nuclei and the middle of the tectum, illustrating some of the tecto-peduncular connections. These fibers are all of medium or thin caliber and, for the most part, unmyelinated. The dendrites of the peduncular neurons ramify widely throughout the entire thickness of the brain wall, and few, if any, of them are in physiological relation with any single one of the afferent systems of fibers. Each of them may be activated by any or all of these systems. The only significant localized specialized tissue here seems to be in the neuropil, where the texture is different in the four layers and where all peduncular neurons spread their dendrites in all these layers. Since the movements which are activated from this motor pool are not disorderly convulsions, it is evident that the discriminative and well co-ordinated responses which follow its excitation are not ordered primarily by the arrangement in space of the motor elements. There are differences in the structural arrangements of the synaptic junctions, though these are not so pronounced as in most other animals, and there may be chemical and other factors yet to be determined. As I have elsewhere pointed out, a time factor can be recognized by physiological experiment, and its structural indicator can be identified histologically because large fibers have a faster rate of conduction than small fibers and the interpolation of synaptic junctions in a nervous pathway retards transmission. In the structural setup before us it may be inferred that the first result of a retinal excitation is the activation of the entire tectum, pretectal nucleus, and dorsal thalamus through the tliick myelinated fibers of the optic nerve and tract and also of the ventrolateral neuropil of the peduncle through the basal optic tract. This is presumably a generalized nonspecific effect, and it will come to motor expression, first, through the basal tract, for this is the shortest path. The resting state is [Begin Page: Page 38] 38 THE BRAIN OF THE TIGER SALAMANDER changed to a state of excitation in both the peduncular gray and the peripheral musculature with which it is connected. This is immediately followed by volleys from the tectum, pretectal nucleus, and thalamus tlirough the myelinated tectoand thalamo-peduncular tracts; and this may contribute a spatial factor determined by the position of the exciting object in the visual field and the sector of the tectum upon which this local stimulus is projected. The first overt movement, accordingly, is an orientation of the body and the eyeballs with reference to the source of stimulus. After an appreciable time the smaller fibers from the retina deliver their volleys, and the small fibers of the correlating tracts are activated. These deliver to the peduncle, not unmixed or purely visual impulses but discharges, fired or inhibited, as the case may be, by the existing excitatory state of the correlating apparatus: and this, in its turn, is determined by numberless nonvisual features of the total situation, present and past. If, for instance, one of the visual or nonvisual components is fatigued, this will affect the pattern of tectal discharge. In salamanders the delay between the preliminary orientation of the body and the consummation of the reaction may be, and commonly is, very long — a period of tension, which in a man we would call "attention" and which Coghill called the "regarding" reaction (p. 78; Coghill, '33, Paper XI, p. 334; '36). During this period an inconceivably complicated resolution of forces is in process within the central apparatus of adjustment. Inhibition plays an important role here, and it may be that the chief function of the ventrolateral superficial neuropil of the peduncle is control of the inhibitory phase of these activities comparable with tliat suggested in chapter xiv for the specific interpeduncular neuropil. Of the details of these adjustments our knowledge is scanty, but some hints may be gathered from urther examination of the structure involved; and here, to simplify the problem, we shall confine tJie discussion to the superficial peduncular neuropil. This neuropil is interpolated "in series" in the visual-motor path of the basal optic tract, and this short circuit is connected "in parallel" with the longer visualmotor circuits by way of the tectum and thalamus. The latter are very much larger and more complicated, and they evidently comprise the major part of the apparatus by which behavior is regulated by visual experience. The basal optic system seems to be ancillary to the major system and to be related with it in two quite different ways, first, as a nonspecific primary activator, as already explained, and, second (and subsequently), as a device for modifying or "inflecting" (to borrow Arnold Gesell's expression) the standard patterns of behavior by intercurrent influence of present activity in other fields, including, perhaps, conditioning and the individuation of hitherto unaccustomed types of response. This second feature involves further consideration of the nonvisual components. These have already been listed, and some of them are shown in figure 23. The largest components of this peculiar neuropil are the optic and tlie visceralgustatory systems, and their fibers end exclusively here. This is why these are regarded as the primary components; all other systems of entering fibers are spread more or less widely also in the deeper layers of peduncular neuropil. In the visceralgustatory system this neuropil is inserted in series in the ascending pathway toward the hypothalamus, and there is probably a parallel system of conduction with no synapse in the peduncle (fig. 8). As seen in tliis figure, peduncular neurons activated from this neuropil send axons around the tuberculum posterius into the hypothalamus; and there is a return path from both dorsal (mamillary) and ventral (infundibular) parts of the hypothalamus to this neuropil and contiguous parts of the peduncle (figs. 18, 'TIS). All visceral-gustatory influences which reach the hypothalamus are, accordingly, previously modified or "inflected" in the superior [Begin Page: Page 39] HISTOLOGICAL STRUCTURE 39 visceral nucleus or in the peduncle. The excitatory state of the hypothalamus, in turn, affects all activity in the peduncle. This sort of circular activity is everywhere present in these urodele brains, working through the diffuse periventricular and deep neuropil and in many places also through specially differentiated tracts (p. 76). This is the primordial apparatus of integration, and in its more differentiated form it is part of the apparatus by which individuated partial patterns of local reflexes are kept in appropriate relationship with the larger total patterns of behavior. In a recent survey ('44o) of tlie optic and visceral nervous circuits here under consideration, several different patterns of linkage of the component units were listed. These include direct activation of eye muscles through the basal optic tract, similar activation of the skeletal musculature, indirect activation of either or both of these sj^stems of muscles by visual stimuli through the tectum and thalamus, direct activation of either or both systems of muscles through the visceral-gustatory path, indirect visceral -gustatory action by way of the superior visceral nucleus, with or without intercurrent influence of the tectum upon this nucleus by way of the tecto-bulbar tract, and the variable effects of concurrent discharge of many other systems of fibers into each of the centers of adjustment involved. Since eacli of these patterns of linkage is complex and the structural units themselves are not simple, it is evident that in actual performance the number of ways in which the known units may be combined and recombined is practically unlimited. The simplest possible activity of stimulus-response type involves a central resolution of forces in an equilibrated dynamic system of inconceivable complexity. Oversimplification of the problem will not hasten its solution. The preceding description illustrates the relations of a specific field of specialized neuropil to other parts of the brain with known functions. These visible connections exhibit a structural arrangement which can be interpreted as putative pathways of transmission of the several components of a complex action system, some concerned with stable reflex patterns and some with more labile individually acquired components. The relations of these two classes of components of the action system to each other and of local units to the integrated whole present the major problems of neurology. [Begin Page: Page 40] CHAPTER IV REGIONAL ANALYSIS SINCE the brain of Amblystoma presents a generalized structure which is probably close to the ancestral type from which all more highly specialized vertebrate brains have been derived, the salient features of internal organization are here summarized in schematic outline. Tlie accompanying diagrammatic figures 1-24 give the necessary topographic orientation, and the details may be filled in by reference to the corresponding sections of Part 11. What is here described may be regarded as the basic organization of the brains of all vertebrates above fishes, that is, the point of departure from which various specialized derivatives have been differentiated. Amblystoma possesses the equipment of sensory and motor organs typical for vertebrates at a rather low level of specialization and in evenly balanced relations. All the usual systems are present, and none shows unusual size or aberrant features. The great lateral-line system of sense organs so characteristic of fishes is preserved, though somewhat reduced after metamorphosis. On the motor side the organs of locomotion and respiration have advanced from the fishlike to the quadrupedal form, but in very simple patterns. In early phylogeny the specialization of the motor systems seems to lag behind that of the sensory systems because the aquatic environment of primitive forms is more homogeneous than that of terrestrial animals, and, accordingly, fewer and simpler patterns of behavior are needed. Our search in this inquiry is for origins of human structures and for an outline of the history of their evolution. From this standpoint it is evident that in the central nervous systems of all vertebrates there is a fundamental and primary difference between the cerebrum above and the rhombencephalon (and spinal cord) below a transverse plane at the posterior border of the midbrain (for further discussion of this see chaps, viii and xiii). The spinal cord and rhombic brain contain the central adjustors of the basic vital functions — respiration, nutrition, circulation, reproduction, locomotion, among others. This apparatus is elaborately organized in the most primitive living vertebrates, as also no doubt it must have been in their extinct ancestors. The cerebrum, on the 40 [Begin Page: Page 41] REGIONAL ANALYSIS 41 other hand, except for the olfactory component, is a hiter acquisition. This is suggested by what is seen in Amphioxus and by the retai-ded development of the cerebrum in all vertebrate embryos, as illustrated especially clearly in the early fetal development of the opossum. At an early (and unknown) period of vertebrate ancestry a pair of eyes was differentiated. These and the olfactory organs are the leading distance receptors, and as such they gave to the vertebrate ancestors more information about their surroundings and hence greater safety in moving about freely. The nose and eyes, with the associated oculomotor apparatus, early assumed the dominant role in the recognition of food, mates, and enemies, and their cerebral adjustors were enlarged accordingly. The contact receptors are adequate for sedentary, crawling, or burrowing ancestors, and here the response to stimulation follows immediately. But, as Sherrington long ago pointed out, in a free-swimming animal there is a time lag between reception of the stimulus from a distant object and the consummation of the response. The pregnant interval between the anticipatory and consummatory phases of the reaction gives the clue to an understanding of the entire history of forebrain evolution. During this interval there is a central resolution of forces, which eventuates in appropriate behavior; and, with increasing complication of patterns of behavior, this central apparatus of adjustment assumes more and more structural complexity and physiological dominance over the entire bodily economy (chap. vii). The details of these internal connections are not relevant here. It suffices to present two summaries, one in this chapter in topographic arrangement by regions from spinal cord to olfactory bulbs as conventionally described and one in the next chapter on a different plan, i.e., an arrangement in longitudinal zones which are functionally defined. For the present purpose it is convenient to recognize seventeen subdivisions of the central nervous system, each of which is characterized by special physiological activities, though these activities are not localized here exclusively. This subdivision might be carried further into detail indefinitely. Numbers 2-6 in the following paragraphs are in the rhombic brain; the others are in the cerebrum. THE SUBDIVISIONS, SPINAL CORD TO PALLIUM 1. THE SPINAL CORD The spinal cord is not described in this report except for some features closely related to the brain, to which reference is made in the next paragraph. The cord segments are organized for the regulation [Begin Page: Page 42] 42 THE BRAIN OF THE TIGER SALAMANDER of local reflexes of the limbs and the integration of these reflexes with one another and with the action of the trunk musculature, as in ordinary locomotion. "l. THE BULBO-SPINAL JUNCTION The sector of the bulbo-spinal junction includes the upper segments of the spinal cord and the lower part of the medulla oblongata. It is the first center of correlation to become functional in embryonic development (Coghill, '14, Paper I). Its dorsal part around the calamus scriptorius receives fibers from the entire sensory zone of the bulb and cord, so that this gray of the funicular and commissural nuclei is a general clearing-house for all exteroceptive, proprioceptive, and visceral functions of the body except vision and olfaction. Here these functions are integrated in the interest of control of posture, locomotion, visceral activity, and other basic components of mass-movement type. Some of these connections are shown diagrammatically in figures 3, 7, 8, 87; for details and discussion see chapter ix and a recent paper ('446). Efferent fibers from the dorsal nuclei are directed spinalward and forward. Most of the latter connect with motor nuclei of the medulla oblongata; some go farther forward to the cerebellum, tectum, and thalamus; and there is a strong, ascending visceral-gustatory tract to the isthmus and peduncle. The motor zone of this sector is occupied chiefly by fibers of passage. The moderately developed gray substance includes motor neurons for muscles of the neck region, for the tongue muscles, and for special visceral motor elements of the accessorius component of the vagus. 3. MEDULLA OBLONGATA The medulla oblongata, or bulb, includes all the stem between the isthmus and the calamus scriptorius except the cerebellum, there being no pons. Its dorsal field receives all sensory fibers from the head except the optic and olfactory, fibers from lateral-line organs widely distributed over the body, and general visceral sensory fibers chiefly by way of the vagus. The general visceral sensory and gustatory root fibers are segregated from the others in the fasciculus solitarius; and this group has its own system of secondary fibers, which converge into the visceral motor nuclei of the medulla oblongata and spinal cord. There is also a strong ascending secondary visceral tract {tr.v.a.) to the isthmus, peduncle, and hypothalamus, through which all cerebral activities may be influenced by visceral and gustatory functions (fig, 8 and chaps, x, xi). [Begin Page: Page 43] REGIONAL ANALYSIS 43 U'lie other afferent fibers of the V to X cranial nerves, upon entrance into the brain, are fascicuhitetl according to the functional systems represented, as outlined in the next chapter and shown in figures 7, 9, 88, 89, 90. The general cutaneous, lateral-line, and vestibular fibers are arranged in a series of fascicles bordering the external surface; the visceral sensory and gustatory fibers are assembled in a single deeper bundle, the fasciculus solitarius. The marginal fascicles of root fibers are arranged from ventral to dorsal in the following order : general somatic sensory (chiefly cutaneous), vestibular, and, dorsally of these, five or six fascicles of fibers of the lateral-line roots of the VII and X nerves. The details of this arrangement are variable within the species and from species to species of urodeles. The fascicles of vestibular and lateral-line roots, together with the underlying gray and the intervening neuropil, comprise the area acusticolateralis. The dorsal part of this, which receives only roots of the lateral-line nerves, is lobulated on the ventricular side. Most of these root fibers divide into ascending and descending branches, and each fascicle spans the entire length of the medulla oblongata. Some of the general cutaneous and vestibular fibers extend far down into the spinal cord and upward into the cerebellum (figs. 3, 7). Terminals and collaterals of all these fibers end in a common pool of neuropil, from which secondary fibers go out to effect local connections in the medulla oblongata, to enter the cerebellum, to descend to the spinal cord, and to ascend in the lemniscus systems to the tectum and thalamus. The physiological specificity of the root fibers i.s largely, though not entirely, obliterated at the first synapse in the neuropil of the sensory field, in sharp contrast with the mammalian arrangement (chap. xi). Prom this arrangement of the sensory systems of fibers and their central secondary connections it is clear that the bulbar structure is so organized as to facilitate mass movements of total-pattern type, which may be activated by any one of the exteroceptive or proprioceptive systems or by any conibination of these. There is some provision here for local reflexes of the muscles of the head, but the structure indicates that most of these are patterned from higher centers. The central receptive field of the visceral-gustatory system is well segregated from that of the general cutaneous and acousticolateral systems; and this is the structural expression of the fundamental distinction between the visceral and the somatic sensory physiological systems, to which further reference is made on pages G7 and 83. [Begin Page: Page 44] 44 THE BRAIN OF THE TIGER SALAMANDER Otherwise, there is httle histological evidence of precise localization of function in the medulla oblongata. The visceral and somatic sensory fields are cross-connected within the sensory zone, and they converge into a common sensory field at the bulbo-spinal junction. Proprioceptive adjustments are made throughout the spinal cord, medulla oblongata, cerebellum, and tectum; and each of these regions evidently plays a different role in the adjustments. Arcuate fibers connect all parts of the sensory zone with the motor zone of the same and the opposite side, and many of these divide into longdescending and ascending branches, thus activating extensive areas of the intermediate and motor zones. The motor field of the medulla oblongata and the intimately related reticular formation contain the complicated apparatus by which the nuclei of the motor nerves are so interconnected as to act in groups, each of which may execute a series of co-ordinated actions in patterns determined by these connections. The tissues of the motor tegmentum, which effect this analysis of motor performance, are so intricately interwoven that it has not been possible to recognize the components of the several functional systems, and further analysis of this field is desirable. 4. CEREBELLUM The cerebellum is small and very simply organized, but the chief structural features of the mammalian cerebellum are present except the pontile system, which is totally lacking. The urodele cerebellum consists of three major parts: (1) the median body, activated from the spinal cord, trigeminal nerve, and tectum (figs. 1, 3, 10); (2) the lateral auricles, which are enlargements of the anterior ends of the sensory zones of the medulla oblongata (figs. 7, 91); and (3), ventrally of the body of the cerebellum, a nucleus cerebelli, which is the primordium of the deep cerebellar nuclei of mammals (figs. 10, 32, 91). This analysis of cerebellar structure is based on the comprehensive studies of Larsell ('20-'47) and Dow ('42), whose descriptions of Amblystoma, published in 1920 and 1932, I have confirmed in all respects. It should be noted that my definition of the amphibian auricle includes more than Larsell's, for he includes in this structure only the vestibular and lateral-line components. I find that these terminals and the related field of neuropil are so intimately related with the terminals of the trigeminus, the visceral-gustatory system, and lemniscus fibers that their segregation is not practical anatomi- [Begin Page: Page 45] REGIONAL ANALYSIS 45 cally. The auricle, accordingly, is here regarded as the common primordium of several structures which in higher animals are diversely specialized for different functions. The most notable of these are the superior or pontile nucleus of the trigeminus and the floccular part of the flocculonodular lobe of the cerebellum. The primordia of these structures are clearly evident, and the history of their further differentiation in higher animals has been written. Efferent fibers of tractus cerebello-tegmentalis leave all parts of the cerebellar complex for the underlying gray; and one fascicle of these — the brachium conjunctivum — passes forward to a ventral decussation and distributes its fibers to the isthmic tegmentum of both sides (figs. 10, 71). No primordium of the nucleus ruber or of the inferior olive has been recognized. This primitive cerebellum exhibits the typical vertebrate pattern in very instructive form, with localization of the vestibular system laterally and the other systems medially. It is an appendage added to the basic sensori-motor systems; it supplements them, not as an aid in determining the pattern of performance, but to insure efficient execution. In species in which it is greatly enlarged, it contains enormous reserves of potential nervous energy, which is released during motor activity to reinforce and stabilize the operation of the effectors. For additional details see chapters x and xii. 5. ISTHMUS The isthmus is unusually large in urodeles and is clearly circumscribed from surrounding parts. Dorsally it is small, containing in and near the superior medullary velum a special segment of the mesencephalic V nucleus and probably other peripheral connections through the nerves of the chorioid plexuses and meninges. Below this there is the superior visceral-gustatory nucleus (figs. 2B, 8, 23, 34). The nucleus isthmi, which is large in the frog, is here undifferentiated. The ventral part of the isthmus is very large, containing the nucleus of the IV nerve and a mass of tegmental cells. This isthmic tegmentum is interpolated between the primary sensori-motor systems of the medulla oblongata and midbrain, and it serves as an intermediary between them. There is a large central nucleus of small cells which receives fibers from a wide variety of correlation centers of intermediate- zone type. These enter by all the dorsal tegmental fascicles and by several other paths (figs. 16, 17, 21). This nucleus is enveloped by a group of larger cells, which is continuous posteriorly with similar tegmental cells of the region of the trigeminus (figs. 29, 30, 91). The [Begin Page: Page 46] 46 THE BRAIN OF THE TIGER SALAMANDER complex as a whole is believed to have two chief functions: (1) Here are organized the patterns of the local reflexes of the musculature of the head, particularly those concerned with feeding. (2) The smallcelled central nucleus is a special differentiation of the periventricular gray, which serves, in addition to the specific functions just mentioned, a more general, nonspecific, totalizing function; that is, it is a part of that integrating apparatus which appears in mammals as the dorsal tegmental nucleus and the related fasciculus longitudinalis dorsalis of Schiitz (p. 208). The details of structure are given in chapter xiii. The isthmic tegmentum occupies a strategic position between the primitive bulbo-spinal mechanisms and the higher cerebral adjustors; it plays a major role both in the patterning of local reflexes and in the integration of all bodily activities. This mass of tissue, which in urodeles is at a low level of differentiation, in higher animals is split up and distributed so that in mammals the identity of the isthmic tegmentum as an anatomical entity is lost in the adult brain, though the isthmic sector is plainly marked in the early embryonic stages. 6. INTERPEDUNCULAR NUCLEUS The interpeduncular nucleus also is unusually large in urodeles. It is not interpeduncular but interisthmic, extending from the fovea isthmi back to the level of the V nerve roots. The histological texture is extraordinary. A well-defined, trough-shaped column of cells borders the ventral angle of the ventricle, with dendrites extending downward through the ventral commissure, to arborize with tufted endings in a ventromedian band of neuropil (figs. 65, 66, 82, 83, 91). The axonic components of this interpeduncular neuropil come from various sources: (1) terminals of the fasciculus retroflexus, which take the form of a flattened spiral (fig. 50); (2) terminals of tr. tegmento-interpeduncularis from small cells of the overlying tegmentum with tufted endings, which join with the dendritic tufts of the interpeduncular nucleus to form small glomeruli (figs. 60-66, 84) ; (3) collaterals of thick fibers of tr. tegmento-bulbaris from the large cells of the tegmentum with similar tufted endings in the glomeruli (fig. 68); (4) collaterals of tr. interpedunculo-bulbaris, which also enter glomeruli (figs. 83, 84) ; (5) terminals of tr. mamillo-interpeduncularis with dispersed free endings (figs. 60, 61); (6) similar terminals of tr. olfacto-peduncularis (fig. 59); (7) less numerous terminals from several other sources. The slender, unmyelinated axons of the interpeduncular cells branch freely in the interpeduncu- [Begin Page: Page 47] REGIONAL ANALYSIS 47 lar neuropil and continue from the nucleus in two strands (figs. 83, 84). The ventral interpedunculo-bulbar tract descends beyond the nucleus for an undetermined distance in the lip of the ventral fissure. The dorsal tract descends dorsally of the fasciculus longitudinalis medialis and turns laterally to end in wide arborizations in the tegmentum as far back as the IX nerve roots. Associated with these dorsal fibers are interpedunculo-tegmental fibers, which end in the neuropil of the isthmic tegmentum. The dorsal and interpedunculotegmental fibers are regarded as comparable with the isthmic and bulbar parts of the mammalian f. longitudinalis dorsalis of Schiitz. The physiological problems suggested by this peculiar structure are puzzling. In the light of such scanty experimental evidence as we possess, I have ventured to suggest that the interpeduncular complex provides both activating and inhibitory components of reflex and general integrative activities, the actual patterns of which are elsewhere determined. Topographically, this nucleus lies in the motor zone, but its functions clearly are of intermediate-zone type. It is present in all vertebrates at the anteroventral border of the isthmus, that is, at the boundary between cerebrum and rhombencephalon. Most of its afferent fibers come from the cerebrum, and evidently it serves chiefly as an intermediary adjustor between the sensory and intermediate zones of higher levels and the motor zone of the rhombic brain (for details see chap. xiv). At this point in our analysis we. cross the boundary between rhombencephalon and cerebrum. The radical differences in structure and physiological properties of these two chief parts of the brain are masked and in large measure overruled, especially in higher animals, by ascending and descending connectives, of which the interpeduncular system is a typical illustration. 7. TECTUM AND PRETECTAL NUCLEUS The tectum and the pretectal nucleus, as sectors of the sensory field, together with the dorsal thalamus, form a physiological unit within which all exteroceptive sensory systems are integrated in the interest of cerebral control of all lower sensori-motor systems involved in the operation of the skeletal musculature. This unit is intimately related with the cerebral peduncle and ventral thalamus. In the most primitive vertebrates and in early embryonic stages of all vertebrates, these structures might appropriately be united as a middle subdivision of the brain, which serves as the dominant center [Begin Page: Page 48] 48 THE BRAIN OF THE TIGER SALAMANDER of cerebral control of all somatic activities. But in the adult animal the parts of this natural subdivision have so many distinctive connections and physiological properties that it seems preferable to treat them separately. In vertebrates below the mammals the tectum opticum is the chief central end-station of the optic nerve; and, since the eyes are the chief distance receptors in most of these animals, fibers of correlation of all other sensory systems concerned with external adjustment naturally converge to this station. The tectum, accordingly, becomes the dominant adjustor of all exteroceptive systems. The tectum mesencephali of Aml^lystoma has a larger optic part — the superior colliculus — and a small, poorly differentiated nucleus posterior — the primordial inferior colliculus. The latter is interpolated between the tectum opticum and the cerebellum, and its connections suggest that its most primitive functions are proprioceptive. It receives a small primordial lateral lemniscus and evidently also serves such generalized auditory functions as this animal possesses (chap. xv). The development of the optic nerve and adult tectal structure and connections have been described in detail ('41, '42). Chapter xvi is devoted to the visual system ; for the arrangement of the mesencephalic nucleus and root of the V nerve see page 140 and figure 13. Optic and lemniscus tracts and smaller numbers of fibers from various other sources all terminate in a broad sheet of intermediate neuropil, which is spread through the entire tectum and is nearly homogeneous in texture (figs. 11, 93). The tectum is not definitely laminated, though separation of the layers, which are conspicuous in the frog, is incipient. Fibers diverge from it in all directions (figs. 12, 18, 21-24, 93). It is inferred from this structure that movements activated directly from the tectum are of total-pattern type. Such local visual reflexes as this animal possesses are probably patterned elsewhere — in the thalamus and dorsal and isthmic tegmentum. Conditioning of reflexes is probably effected in these areas and perhaps also in the ventrolateral peduncular neuropil (p. 38). Experiments upon Triturus and anurans (Stone and Zauer, '40; Sperry, '43, '44, '45, '456) demonstrate anatomical projection of retinal loci upon the tectum opticum. This is true also in Amblystoma (Stone, '44; Stone and Ellison, '45), though the nervous apparatus employed has not been described. The pretectal nucleus (figs. 2B, 35, 36, nuc.pt.) receives fibers directly from the retina and from the tectum, habenula, and cerebral [Begin Page: Page 49] REGIONAL ANALYSIS 49 hemisphere. Its efferent fibers go to the tectum, thalamus, hypothalamus, and cerebral peduncle (figs. 11, 12, 14, 15, 16, 22, 23). Its functions are unknown, but, by analogy with mammals, this may be part of the apparatus for regulation of the intrinsic musculature of the eyeball. Doubtless other functions are represented also. This area is the probable precursor of the mammalian pulvinar and neighboring structures. The thalamus receives many fibers from the retina, and it is broadly connected with the tectum by uncrossed fibers passing in both directions in the brachia of the superior and inferior colliculi (figs. 11, 12). There are also systems of tecto-thalamic and hypothalamic and thalamo-hypothalamic tracts which decussate in the postoptic commissure ; some of these crossed fibers take longer courses to reach the peduncle and isthmic tegmentum (figs. 12, 15). This intimate thalamo-tectal relationship is radically changed in higher animals, where the thalamo-cortical connections are highly elaborated. 8. DORSAL THAL.\MUS I have separated the dorsal thalamus into three sectors: (1) anteriorly, the small nucleus of Bellonci of uncertain relationships ; (2) a well-defined middle part, an undifferentiated nucleus sensitivus, which is the primordium of most of the sensory nuclei of the mammalian thalamus; and (3) a vaguely delimited posterior sector, which apparently contains the undifferentiated primordium of both lateral and medial geniculate bodies (chap. xvii). The middle and posterior sectors receive numerous terminals and collaterals of the optic tracts, terminals of the general bulbar and spinal lemnisci, and, through the brachia of the superior and inferior colliculi, these sectors are broadly connected with the tectum by fibers running in both directions. There is a similar, but much smaller, connection with the habenula. From the middle sector a small, well-defined tr. thalamo-frontalis goes forward to the hemisphere (figs. 15, 71, 72, 95, 101, tr.th.f.); this is the common primordium of all the thalamo-cortical projection systems of mammals, though here few, if any, of its fibers reach the pallial area. Other efferent fibers go to the ventral thalamus, hypothalamus, peduncle, and tegmentum. These thalamic reflex connections antedate in phylogeny the thalamo-cortical connections, and they persist in mammals as an intrinsic paleothalamic apparatus, an important part of which is the periventricular thalamic contribution to the f. longitudinalis dorsalis of Schiitz. The largest pathwaj^s [Begin Page: Page 50] 50 THE BRAIN OF THE TIGER SALAMANDER of efferent discharge from the dorsal thalamus go backward to the peduncle and tegmentum by both crossed and uncrossed tracts (figs. 15, 18, 21, 23). The peduncular connection puts all the primary systems of total-pattern type under some measure of thalamic control. The connections with the dorsal and isthmic tegmentum probably co-operate in the patterning of local reflexes, particularly supplying the visual component of the feeding reactions. 0. PEDUNCLE The "peduncle" described here is not the equivalent of the human cerebral peduncle (p. 21). The intimate relations of this field with the overlying tecto-thalamic field have been commented upon in the preceding paragraphs. This ventral field is a well-defined column of cells, differentiated at the anterior end of the basal plate of the embryonic neural tube. It is the head of the primary motor column (of Coghill), which in all vertebrates, from early embryonic stages to the adult, contains the nucleus of the oculomotor nerve and a much larger mass of nervous tissue, which activates the primitive mass movements of locomotion. It maintains cerebral control of the lower bulbo-spinal segments of the latter systems, and some other motor functions also are represented here. Into it fibers converge from all other parts of the cerebrum (figs. 12, 14, 15, 17, 18, 20-24), and from it efferent fibers go out in four groups: (1) Ventromedial tracts go to the medulla oblongata and spinal cord. The longest of these fibers are in the f. longitudinalis medialis (fig. 6). (2) The oculomotor nerve supplies intrinsic and extrinsic muscles of the eyeball (figs. 22, 24). Associated with these peripheral fibers are central connections with the nuclei of the IV and VI nerves, so arranged as to execute conjugate movements of the eyes. The details of the apparatus employed are unknown. (3) Visceral sensory and gustatory fibers enter the peduncle (fig. 8), and with these are related efferent fibers to the hypothalamus and to lower levels of the motor zone, The pathways taken by the latter in the amphibian brain have not been clarified. (4) From both ventral thalamus and peduncle, fibers diverge to various surrounding parts, notably to the hypothalamus and isthmic tegmentum. These probably provide for co-ordination of various local reflex activities with the basic peduncular functions. At the ventrolateral border of the peduncle there is an area of superficial neuropil, which is the terminus of the basal optic tract, large secondary and tertiary visceral-gustatory tracts, some fibers of the f. retroflexus, and fibers from several other sources (figs. 22, 23, [Begin Page: Page 51] REGIONAL ANALYSIS 51 24). This is an undifferentiated primordium of the basal optic nucleus and some other structures of the mammalian brain (pp. 35, 221). It is related with the olfacto-visceral functions of the hypothalamus and probably also with conditioning of the fundamental peduncular activities. 10. VENTRAL THALAMUS There are anterior and posterior sectors of the ventral thalamus which differ in embryological origin (p. 239) and in certain connections of intermediate-zone type. Both sectors are here included in the motor zone because their chief efferent connections resemble those of the "peduncle," of which the posterior part is physiologically an anterior extension. The ventral thalamus is the primordium of the motor field of the mammalian subthalamus. The anterior sector contains a nucleus specifically related to the stria medullaris and amygdala and, above this, the eminentia thalami, which is a bednucleus of tracts related to the primordium hippocampi (chap, xviii; figs. 16, 17, 19, 20, 96). The ventral thalamus and peduncle of urodeles form a single massive column, which is anatomically well defined. The specialized structures derived from it in mammals are dispersed among large masses of tissue of more recent phylogenetic origin; but in the human brain this region still retains cerebral control of the primordial coordinated movements of the musculature of the eyeballs and of the trunk and limbs. 11. THE RETINA AND ITS CONNECTIONS In early embryonic stages the retina is part of the brain, and, as development advances, it absorbs much of the diencephalic sector of the early neural tube. This precociously accelerated development results from the dominance of vision in exteroceptive adjustment from the time that the larva begins to feed. For further details of this development and of the organization of the visual-motor apparatus see chapter xvi. 1-2. IIABEN(jL.\ As described in chapter xviii, this specialized part of the epithalamus receives fibers from almost all parts of the telencephalon and diencephalon and from the tectum (fig. 20). The habenular commissure connects the two habenulae, and it also contains two commissures of pallial parts of the hemispheres — commissura pallii posterior and com. superior telencephali. The chief efferent path from the [Begin Page: Page 52] 52 THE BRAIN OF THE TIGER SALAMANDER habenula is the f. retroflexus (chap, xviii), which terminates in the cerebral peduncle and interpeduncular nucleus. In the brains of lower vertebrates the habenular complex is one of the most widely spread and physiologically important members of the central correlating apparatus. Its primary function seems to be to integrate the activities of all parts of the brain that are under olfactory influence with the exteroceptive functions of the tectum and thalamus in the interest of higher cerebral control of the feeding reactions of the skeletal muscles. 13. HYPOTHALAMUS In the large preoptic nucleus and hypothalamus, olfactory connections dominate the picture, as they do in the habenular system; but here the nonolfactory functions represented are interoceptive instead of exteroceptive. All parts of the cerebral hemisphere are connected with the hypothalamus by fibers passing in both directions in the medial forebrain bundles (p. 273), stria terminalis (p. '^55), and fornix (p. 254) systems. The visceral-gustatory afferent paths are shown in figure 8. Large tracts from the thalamus and tectum also end here, so that all kinds of sensory experience of which the animal is capable are represented in the hypothalamus. This experience is here organized in terms of visceral responses. The efferent tracts go to the peduncle, tegmentum, interpeduncular nucleus, and descending fibers in the deep neuropil which are precursors of the f. longitudinalis dorsalis of Schiitz. There is a large tract to the hypophysis for nervous control of endocrine activity. There is also evidence that some neuro-endocrine functions are performed in the hypothalamus itself (Scharrer and Scharrer, '40). The structure of the hypothalamus has been described ('21a, '27. ''^5a, '36, '42, and in the embryological papers, '37-'41). It is similar to that of Necturus, of which more detailed descriptions have been published ('336, '346). For the composition of the postoptic commissure see chapter xxi. 14. STRIO-AMYGDALOID COMPLEX The primordial corpus striatum occupies the thickened ventrolateral wall of the cerebral hemisphere and, like all the rest of the hemisphere, is under olfactory influence. This is stronger at its anterior and posterior ends. Anteriorly, it is divided by a striatal sulcus into dorsal and ventral parts (fig. 99), and posteriorly it is much enlarged as the amygdala (figs. 1, 96, 97), which has the typical mammalian connections (fig. 19). [Begin Page: Page 53] REGIONAL ANALYSIS 53 The ventral sector of the anterior olfactory nucleus is interpolated between the olfactory bulb and the corpus striatum, as in Necturus (figs. 6, 86). This is the primordium of the tuberculum olfactorium ('27, p. 290), which is enormously enlarged in the lungfishes (Rudebeck, '45). Posteriorly of this nucleus is a poorly defined field, which embraces the ventral angle of the lateral ventricle and is regarded as the probable precursor of the head of the caudate nucleus (fig. 99) It is intimately connected with the rest of the striatum and the septum. The chief efferent path is the olfacto-peduncular tract to the dorsal hypothalamus, ventral border of the peduncle, and interpeduncular nucleus. The middle sector of this complex is the undifferentiated primordium of the mammalian lentiform nucleus, as shown by its fibrous connections. It is characterized by very dense, sharply circumscribed neuropil in the white substance (p. 96; figs. 98, 99, 108, 109) and has the typical striatal connections with the overlying pallium and the thalamus, including a small sensory projection tract from the dorsal thalamus (fig. 15, tr.th.f.). The chief efferent path is the lateral forebrain bundle (f. lateralis telencephali, /.Za^./.), which contains strio-thalamic, strio-peduncular, and strio-tegmental fibers comparable with the corresponding components of the mammalian extrapyramidal system. There is also a strio-tectal and strio-pretectal connection (figs. 11, 14, 101). The separation of the lentiform nucleus into globus pallidus and putamen is incipient (p. 97). 15. SEPTUM The septum complex occupies the ventromedial wall of the hemisphere between the anterior olfactory nucleus and the lamina terminalis and hippocampal area (figs. 4, 98, 99) . Its position and connections are similar to those of mammals. It is directly connected with the olfactory organ by the nervus terminalis, and it receives fibers from the olfactory bulb, anterior olfactory nucleus, pallium, and hypothalamus. The chief efferent paths are by the medial forebrain bundle (f . medialis telencephali, f.med.t.) and to the overlying pallium by the f. olfactorius septi ('27, p. 291). There is also a broad connection across the ventral aspect of the hemisphere with the amygdala and the piriform area, the diagonal band of Broca (figs. 96, 97, 98, d.b.), and a connection with the habenula by tr. olfactohabenularis anterior and tr. septo-habenularis (chap, xviii). [Begin Page: Page 54] 54 THE BRAIN OF THE TIGER SALAMANDER 16. OLFACTORY BULB AND ANTERIOR OLFACTORY NUCLEUS The olfactory bulb is very large, embracing the anterior end of the lateral ventricle and extending back in the lateral wall for about half the length of the hemisphere (figs. 1, 3, 4, 85, 100, 105, 110; '246, '27). All peripheral olfactory fibers end in the glomeruli of the bulb. Fibers of the second order pass in large numbers to the anterior olfactory nucleus, and they enter longer olfactory tracts with wide distribution (fig. 6), The olfactory tracts are mixtures of fibers from the bulb and the anterior nucleus, as in Necturus ('336, figs. 6 16). They reach all parts of the cerebral hemisphere, the habenula, and the hypothalamus. Some of these decussate in the ventral part of the anterior commissure and some in the habenular commissure (com. superior telencephali). The histological texture of the olfactory bulb is more differentiated than that of Necturus ('31), but more generalized than that of higher vertebrates. I have contrasted this with the mammalian pattern and added a theoretic interpretation of probable differences in physiologic properties of the tissue ('246). In brief, this tissue is interpreted as illustrating several transitional stages in the differentiation of polarized nervous elements from an unpolarized or incompletely polarized matrix. In Necturus ('31) the transitional character of this tissue is still more clearly evident. The granule cells, in particular, give no structural evidence of physiological polarity, i.e., of differentiation of dendrites from axon, though the connections of these cells in Amblystoma suggest that they have a transient and reversible polarity. In connection with this description ('246, pp. 385-95) there are some speculations regarding possible phylogenetic stages in the differentiation of permanently polarized neurons from an unspecialized nonsynaptic nerve net or neuropil. In Amblystoma there is a moderately developed accessory olfactory bulb, but no other evidence of local specialization in the primary olfactory center. (There are hints of this in some mammals, e.g., the mink, Jeserich, '45, and references there cited). In 1921, I described the peripheral and central connections of the accessory bulb of Amblystoma and compared these with the more specialized structures of the frog. The anatomical connections there described are, I believe, correct, but the theoretic interpretation of the relationships in vertebrates generally between the vomeronasal organ, accessory [Begin Page: Page 55] REC.IONAL ANALYSIS 55 bulb, and amygdala is less secure and awaits confirmation or correction. The anterior olfactory nucleus is a zone of relatively undifferentiated cells interpolated between the bulbar formation and the more specialized areas posteriorly of it (figs. 6, 86B and C, 105, 109; '27, p. 288). In higher animals much of this tissue seems to be specialized and added to the adjoining fields ('24(/). A very large proportion of the fibers of the olfactory tracts, arising from both the bulbar formation and the anterior nucleus, are assembled in a dense superficial sheet of fibers in the medial sector of the anterior olfactory nucleus, which I have named the "fasciculus postolfactorius" (figs. 5, 100, 105, 110, /./JO.). Here these fibers take a vertical course and then are distributed to all the olfactory tracts. In chapters vii and xix there is further discussion of the significance of the olfactory system in the morphogenesis of the hemisphere. 17. PALXiIUM The pallial part of the hemisphere can be distinguished from the stem part, though there is no laminated cortex. There are three sectors (figs. 96-99) — the dorsomedial primordium hippocampi {p.hip.), the dorsolateral primordium piriforme {p.pir., or nucleus olfactorius dorsolateralis, nuc.oLd.L), and between these a dorsal sector of uncertain relationships (p.p.d.). The gray, as elsewhere in these brains, is confined to a thick periventricular layer except in the hippocampal sector, where the cell bodies are dispersed through the entire thickness of the wall and are imbedded in dense neuropil. This is evidently a first step toward differentiation of superficial cortex. The homologies of the hippocampal and piriform sectors with those of mammals are clear, as shown by substantially similar nervous connections. Further discussion will be found in chapter vii and the references there given. THE COMMISSURES Throughout the length of the central nervous system all parts of the two sides are broadly connected by systems of commissural and decussating fibers. These are in two series, dorsally and vent rally of the ventricles. Their composition is summarized in chapter xxi, with references to more detailed descriptions. In the aggregate they make provision for the co-ordinated action of the motor organs on right and left sides of the body. [Begin Page: Page 56] 56 THE BRAIN OF THE TIGER SALAMANDER CONCLUSION The preceding outline of a regional analysis is framed in very general terms. The evidence upon which it is based is assembled in Part II of this work and references there given. This evidence, though far from complete, is regarded as adequate for the anatomical arrangements described. The physiological inferences drawn from these arrangements and the general theory expressed in the following chapters rest on a less secure basis. The correctness of these conclusions can be tested experimentally, and the hope that this will be done has motivated the labor expended upon this program of histological study. [Begin Page: Page 57] CHAPTER V FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL THE brain of Amblystoma performs three general classes of functions, with corresponding local differentiation of structure. We recognize, accordingly, three zones on each side — a dorsal receptive or sensory zone; a ventral emissive or motor zone; and, between these and infiltrating them, an intermediate zone of correlation and integration. THE LONGITUDINAL ZONES Figures 4 and 5 are sketches of longitudinal sections of the cerebrum of adult Amblystoma tigrinum to illustrate the areas included in the motor and sensory zones as here arbitrarily defined. The zones of the medulla oblongata as seen in transverse section are shown in figure 9. The sensory zone includes those parts of the brain which receive afferent fibers from the periphery, together with more or less closely related tissue of correlation. The motor zone includes those parts from which efferent fibers go out to the periphery, together with related apparatus of motor co-ordination. Both these zones contain some areas which, though not directly connected with the periphery, are nevertheless primarily concerned with specific types of sensory or motor adjustment. What is left over is assigned to the intermediate zone, and whether a particular area will be included here depends on one's estimate of its preponderant physiological character. The body of the cerebellum and the pallial part of the cerebral hemispheres are excluded from the zones as supra-segmental structures. The lines drawn in this analysis are frankly arbitrary, chosen primarily for convenience of description; but, as will appear, this functional analysis contributes to an understanding of the meaning of the structure, and, moreover, it has morphological justification as well. These zones are not autonomous units when viewed either structurally or physiologically. Their interconnections are intimate and complicated. The more important of these connections are shown in 57 [Begin Page: Page 58] 58 THE BRAIN OF THE TIGER SALAMANDER a number of diagrams, some in this contribution and some in previous papers. This analysis of the more obvious structural features of an amphibian brain in terms of physiological criteria is an artificial schematization of a complicated fabric, the several parts of which are so intimately connected that there is an over-all integration of their activities. The main highways of through traffic have been mapped, with signboards pointing the way at the crossroads. Selected examples of some of the lines of fore-and-aft through traffic are illustrated in the diagrams ; but this kind of analysis does not take us to our destination. It does not tell us how mixed traffic is actually sorted out and so reorganized as to give the body as a whole efficient adjustment to the momentarily changing exigencies of common experience. These problems are discussed in subsequent chapters, but, first, the schematic outline will be summarized here. Each zone is structurally diversified, and many of these local differentiations are directly correlated on the sensory side with the modalities of sense represented in the end-organs with which they are connected and on the motor side in a similar way with synergic systems of muscles. Each sensory and motor system of nerves has a local primary central station in direct connection with the periphery, and each of these stations has widely spread connections within its own zone and with other zones, thus insuring efficient correlation of sensory data, co-ordination of motor responses, and integration of the action system as a whole. In this summary the sensory systems are given special attention because these are the most useful guides in the analysis of the structure of this brain. THE SENSORY ZONE The sensory zone is defined as those parts of the brain that receive fibers from peripheral organs of sense. In some fields the number of such fibers is large, in others it is very small; and some parts of the brain, like the cerebral peduncle, have both sensory and motor peripheral connections. Within the sensory zone there is a complicated apparatus of correlation, and in lower vertebrates the receptive areas and surrounding tissues dominated by them are so large that most of the mass of the brain can be blocked into fields appropriately designated "nosebrain," "eyebrain," and so on ('31a, p. 129). This feature is due to the fact that in these animals the sense organs are well developed and highly specialized, but the motor apparatus is [Begin Page: Page 59] FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL 59 more simply organized, chiefly for co-ordinated mass movements. The sensory zone with its own apparatus of correlation, accordingly, bulks larger than the motor zone. Though the peripheral sensory apparatus in Amblystoma differs from the human in many details, yet the general principles of its organization are similar; the structural organization of the central apparatus of adjustment, on the contrary, is so radically different that comparisons are difficult. Here the several functional systems of peripheral nerve fibers enter the brain in fascicles of the nerve roots, which are physiologically as specific as are those of mammals ; but at the first synapse this specificity may almost completely disappear, in so far as it has visible structural expression. The root fibers of all sensory systems (except, perhaps, the olfactory) terminate by wide arborizations in a few common fields of neuropil, in each of which several of these systems are inextricably mingled. This neuropil is a common synaptic pool for all entering systems. The several pools are interconnected with one another and with similar pools in other parts of the brain stem, and there is no supreme cortical regulator. The translation of sensory experience into adaptive behavior and the integration of this behavior are somehow accomplished within this interplay of the local activities of the brain stem. The sensory zone is continuous from the dorsal gray colunm of the spinal cord to the olfactory field, comprising the dorsolateral part of the medulla oblongata, the auricle in the cerebellar region, the anterior medullary velum and a small amount of contiguous tissue, the tectum of the midbrain, pretectal nucleus, dorsal thalamus, olfactory bulb with the adjoining anterior olfactory nucleus, and optionally the septum and some other parts of the hemisphere, a portion of the hypothalamus, and the ventrolateral neuropil of the peduncle. The fields optionally included receive terminals of the nervus terminalis (p. 267); the hypothalamus has a small but significant connection with the optic nerve, the basal root of which also connects with the peduncle. In some vertebrates the epithalamus receives fibers from the parietal eye, but in Amblystoma these have not been seen, and in this animal the predominant functions of the "optional" areas are of intermediate-zone type. The body of the cerebellum and the pallial part of the cerebral hemisphere might be assigned to the sensory zone as here defined anatomically; yet, as previously mentioned, they are excluded from this zone because of their distinctive physiological characteristics and their remarkable specialization in higher animals. [Begin Page: Page 60] 60 THE BRAIN OF THE TIGER SALAMANDER In the sensory zone of the medulla oblongata there are two elongated synaptic pools of neuropil, into which terminals of the sensory root fibers converge (chap. xi). One of these receives terminals of all somatic sensory systems; the other lies more ventrally and internally in the visceral lobe and receives terminals of the visceral sensory and gustatory systems (figs. 9, 89). The secondary fibers which emerge from these pools are distributed locally to the motor zone of the medulla oblongata, downward to the spinal cord, and upward to higher levels. The last take different courses, some to the cerebellum, some to the tectum and thalamus, and some to the hypothalamus. Each of these pathways discharges into a higher synaptic pool of neuropil, where its terminals are in physiological relation with terminals of other related sensory systems. The relations to which reference has just been made are in terms of the types of response to be evoked. Thus the tectum becomes the dominant regulator of somatic adjustments to exteroceptive stimulation, the hypothalamus becomes the regulator of visceral responses to olfacto-visceral stimulation, and the cerebellum provides regulatory control of the action of the skeletal muscles. The dorsal thalamus is ancillary to the tectum and shows a very early stage in the evolution of the ascending sensory projection systems to the cerebral hemispheres. These local differentiations, each with characteristic structure and connections, are receptive fields for the several systems of peripheral sensory fibers, though some of them receive few peripheral fibers and are concerned chiefly with sensory correlation. THE MOTOR ZONE The motor zone as here defined includes the peripheral motor neurons and those areas of the brain stem concerned with the organization of motor impulses in patterns of synergic action. It includes the following histologically different parts: (1) corpus striatum (paleostriatum); (2) anterior part of the ventral thalamus; (3) posterior part of the ventral thalamus; (4) nucleus of the tuberculum posterius ("peduncle" in the restricted sense); (3) isthmic tegmentum; (6) trigeminal tegmentum; (7) a poorly defined tegmental field extending farther posteriorly through the length of the medulla oblongata into continuity with the ventral gray column of the spinal cord. The floor plate of the embryonic neural tube probably ends anteriorly at the fovea isthmi (fig. 2B, f.i.), and the adjacent basal [Begin Page: Page 61] FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL 61 plate, which is the primordial motor zone, extends forward of this to include the whole of the peduncle and probably more or less of the hypothalamus and ventral thalamus. This primordial zone contains not only nervous elements with peripheral connections, like the sensory zone, but also an elaborate apparatus of central co-ordination of the neuromotor systems. Anteriorly of the peduncle the motor zone has no peripheral connections, but the apparatus of motor co-ordination extends forward through the thalamus into the lateral wall of the hemisphere. Since the present analysis is based primarily on physiological criteria, this anterior extension of the motor field is included in the motor zone. The anterior boundaries of this zone are, of course, arbitrarily drawn ; that they are artificial is emphasized by the fact that the large basal optic root terminates in the peduncle, which is in the motor zone as here defined. Efferent fibers have been described as leaving the brain in many places outside the motor zone, even as here broadly defined. Vasomotor and other visceral efferent fibers have been reported in various animals associated with the nervus terminalis and the olfactory and optic nerves and in other places for distribution to meninges and chorioid plexuses. We have nothing new to report about Amblystoma in this connection. In the spinal cord and medulla oblongata the peripheral motor neurons are so mingled with the co-ordinating neurons of the tegmentum and reticular formation and they are so similar in form that it is often impossible to distinguish the peripheral neurons except in cases where their axons are seen to enter the nerve roots. The cells of the nuclei of the eye-muscle nerves are fairly clearly segregated, and in some reduced silver preparations they react specifically to the chemical treatment (fig, 104); but even here their dendrites are widely spread and intertwined with those of tegmental cells, so that both kinds of neurons would appear to be similarly activated by the neuropil within which they are imbedded. The cell bodies are locally segregated; but their dendrites, where most of the synaptic contacts are made, are not segregated. In the medulla oblongata the motor tegmentum contains small and large cells in an endless variety of forms, but these elements are not segregated in accordance with either size or morphological type. It is true that the arrangement of their cell bodies may show some rather ill-defined local segregation, but their dendrites and axons are so intimately intertwined in the neuropil that nothing comparable [Begin Page: Page 62] 62 THE BRAIN OF THE TIGER SALAMANDER with the localized nuclei of higher brains can be recognized. Farther forward in the isthmus and peduncle the tegmental tissue of coordination is much increased in amount and somewhat more differentiated. In some of my former papers (e.g., '30, p. 76) the term "nucleus motorius tegmenti" was used loosely (and inaccurately) to include a tegmental zone defined topographically. This seemed to be justified in the case of Necturus by the lack of localization of the large motor elements which characterize this region; but this justification is inadequate, both factually and morphologically — see the discussion by Ariens Kappers, Huber, and Crosby ('36, pp. 653, 666). It is obvious that most of the tissue of the motor zone is concerned with co-ordination of the action of the peripheral elements, so that synergic groups of muscles are activated in appropriate sequence; but, with the technic available, it has not been possible to analyze this complex so as to reveal the mechanism employed. In the medulla oblongata this organization is chiefly for local control of bulbar and spinal reflexes, the intermediate zone participating. In the isthmus and peduncle the number of peripheral elements is relatively small and the co-ordinating apparatus larger, giving these areas control over all motor fields spinal ward of them. This intrinsic motor apparatus is supplemented by a segregated band of correlating tissue in the intermediate zone, the subtectal dorsal tegmentum. In mammals both these zones are further specialized into separate nuclei distributed in the tegmentum. The primary patterns of somatic movements are predetermined by the course of central differentiation within the motor and intermediate zones in premotile stages of development. After connection with the peripheral musculature is established, each of these muscles seems to exert some sort of distinctive reciprocal influence upon that motor field of the central nervous system from which its innervation is derived. The nature of this influence is unknown, but its reality is well attested by experiments of Paul Weiss ('36, '41) and colleagues upon "myotypic response" and "modulation." In later stages the primary motor patterns may be modified, or "inflected," by sensory experience and practice. Influence of use or some other functional factors seem to be essential for maintenance of motor efficiency, as graphically shown by Detwiler's observations ('45, p. 115; '46) on the behavior of decerebrate larvae of Amblystoma (to which further reference is made on p. 118). In young larvae of stage 37, swimming movements may be perfectly executed [Begin Page: Page 63] FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL (»3 after transection immediately below the auditory vesicle under control of the lower medulla oblongata and spinal cord (Coghill, '26, Paper VI, p. Ill; '29, p. 15); but, subsequent to Harrison's stage 40, Detwiler finds that sustained motor activities, including swimming, fail rapidly if the influence of the midbrain is blocked in prefunctional stages, though feeding reactions are preserved after complete ablation of hemispheres and visual organs. The midbrain evidently supplies a factor essential for maintenance of motor efficiency. The motor field of this brain is smaller and more simply organized than the sensory field because most of the activities are mass movements of total-pattern type. Within this larger frame of total behavior, the partial patterns of local reflexes are individuated with more or less capacity for autonomous action. The number of these local partial patterns is smaller than in higher animals, and all of them are far more closelj^ bound to the total patterns of which they are parts. The segments of each limb, for instance, may, upon appropriate stimulation, move independently; but in ordinary locomotion they move in a sequence related to the action of the entire limb, the other limbs, and the musculature of the trunk. The peripheral motor nerves (omitting the general visceral components of preganglionic type not here considered) are in three groups: (1) the spinal nerves; (2) the eye-muscle nerves. III, IV, and VI pairs of cranial nerves, which are somatic motor; and (3) the special visceral motor nerves of the V, VII, IX, and X pairs, innervating the striated musculature of the visceral skeleton of the head. The primary movements of trunk and limbs are organized for locomotion in the motor zone of the spinal cord. This organization is under exteroceptive and proprioceptive control locally throughout the length of the cord and more especial!}^ at the bulbo-spinal junction; it is under additional proprioceptive control from the labyrinth and the cerebellum; there is further control from the cerebrum — optic, olfactory, and the related apparatus of higher correlation. The bulbar group of special visceral motor nerves is primarily concerned with movements of the head, notably those of respiration and feeding. The feeding reactions are under visual, olfactory, somesthetic, gustatory, and general visceral afferent control, and the pattern of performance seems to be organized in the large isthmic tegmentum. The very large and complicated interpeduncular nucleus is an isthmic structure which is physiologically of intermediate-zone type (chap. xiv) . Details of the structure and connections of the various parts of [Begin Page: Page 64] 64 THE BRAIN OF THE TIGER SALAMANDER the motor zone are in Part II, and the pecuhar features of its forward extension in the cerebral hemisphere are discussed in chapter vii. THE INTERMEDIATE ZONE The characteristics of this zone are imphcit in the preceding account of the sensory and motor zones. It is more elaborately developed and its boundaries are more clearly defined in parts of the cerebrum than in the rhombencephalon. These boundaries are necessarily arbitrary, for all parts of the brain are involved in correlation and integration of bodily activities ; but throughout the length of the spinal cord and brain there is a band of tissue between the sensory and motor zones primarily concerned with these adjustments. At lower levels I have termed this tissue the "reticular formation," and here it infiltrates the other zones with no clear boundaries (for details see chap. xi). At higher levels it increases in amount and is more clearly segregated. It would be appropriate to include in this zone most of the diencephalon and telencephalon except the specific optic and olfactory terminals ; but, for reasons mentioned above, a different subdivision has been adopted, primarily for convenience of description. The dorsal tegmentum, or subtectal area, is a typical representative of this zone in position and physiological connections. In the isthmic and bulbar tegmentum the characteristics of the intermediate and motor zones are inextricably mingled. The habenula, hypothalamus, and interpeduncular nucleus, as elsewhere described, clearly belong physiologically to the intermediate zone; and the whole cerebral hemisphere, except the olfactory bulb, might appropriately be so classified in all Ichthyopsida. In the most primitive vertebrates the intermediate zone is scarcely recognizable as an anatomical entity. As the action system becomes more complicated in higher animals, this zone shows corresponding differentiation. This specialization is more directly dependent upon complication of the peripheral motor apparatus than upon sensory differentiation, for, so long as the action system is largely confined to mass movements, the patterning of these total activities is effected in the sensory and motor zones. In tetrapods and birds more complex central adjustors are required, and these are differentiated between the two primary zones and anteriorly of them. With the appearance of more autonomy of the local reflex systems, more efficient apparatus of integration is demanded. The final result is that in the human brain the apparatus of intermediate-zone type has increased so much [Begin Page: Page 65] FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL G5 that it comprises more than half the total weight of the brain, for both cerebral and cerebellar cortices are derivatives of this primordial matrix, as will appear in the ensuing discussions. THE FUNCTIONAL SYSTEMS The preceding physiological analysis of the brain obviously rests upon the peripheral relations of its several parts. The two primary functions of the nervous system are, first, the maintenance of the integrity of the individual, with efficient co-operation of parts among themselves and with the total organization, and, second, the analysis of experience and the translation of the sensory data into appropriate behavior. The peripheral nerves are key factors in both these domains. Our knowledge of the functional analysis of the cranial nerves has been greatly increased during the last fifty years, largely by the work of the so-called American school of comparative neurologists, which I have recently reviewed ('43). Before I discuss the components of these nerves, a few definitions are in order. In the attempt to envisage the nervous system from the operational standpoint, distinctions have been drawn between sensory correlation, motor co-ordination, and those central processes that provide integration, and some measure of spontaneity of action which might be grouped under the name "association" ('24c, p. 235; '31a, p. 35). This classification is necessarily artificial, for all these processes are interrelated. They interpenetrate, and they are not sharply localized in the structural fabric. Nevertheless, these several types of action are recognizable components of the unitary dynamic system, and there are local differentiations of the structural organization correlated with preponderance of one or another of them, more clearly so in higher vertebrates than in lower. Sensory correlation, as the term is here employed, refers to interaction of afl^erent impulses within the sensory zone, that is, within the field reached by terminals oi peripheral sensory fibers. The interplay of these diverse afi'erent impulses takes two forms: (1) in fields of undifferentiated neuropil, the activation of which results in alterations of the central excitatory state or in mass movements of large numbers of synergic muscles; (2) in more restricted areas (nuclei), which activate the neuromotor apparatus of local reflexes. The members of both groups are interconnected by systems of internuclear fibers like the lemniscus systems, all within the sensory zone, so that all activities of this zone interact one with another. These inter- [Begin Page: Page 66] 66 THE BRAIN OF THE TIGER SALAMANDER nuncials are so arranged that functional systems of afferents, which normally co-operate to effect a particular type of motor response, are more intimately associated. Thus the tectum opticum receives most of the lemniscus fibers of all somesthetic systems and minimum numbers of olfactory and visceral systems. This basic pattern as seen in Ambly stoma is changed in mammals, where higher associational centers have taken over most of the functions of correlation. Motor co-ordination is effected primarily in the motor zone, which is so organized as to activate synergic groups of muscles in appropriate sequence with inhibition of their antagonists. This grouping may be adapted for mass movements or for local reflexes. Internuclear tracts connect the various parts of the sensory zone directly with appropriate parts of the motor zone. More refined analysis and conditioning of motor responses are effected through the intermediate zone, and the tissues of the latter group are greatly enlarged and complicated in higher brains. The activities of stimulus-response type which have just been considered are so interconnected with internuclear tracts and the interstitial neuropil as to facilitate the integration of all local activities in the interest of the requirements of the body as a whole. Every local part of the brain is a component of the apparatus of general integration, and some of these parts have this association as their dominant function. In Ambly stoma most of this suprasensory and supramotor tissue is dispersed as interstitial neuropil. In mammals, higher types of associational tissue have been differentiated locally, notably in the cerebral cortex and its dependencies, with corresponding enhancement of those synthetic functions which are manifested as conditioning, educability, and reasoning. Parallel with these changes there is an enormous increase in accumulated reserves of potential nervous energy, which come to expression as spontaneity, memory, and creative imagination. A survey of the nerve fibers of Amblystoma as a whole in view of the principles just expressed shows that they may be classified in four groups: (1) the peripheral afferent systems and associated internuclear correlating tracts within the sensory zone (lemniscus systems, etc.) ; (2) the peripheral efferent systems and the related coordinating fibers of the motor zone; (3) the central internuclear systems intercalated between the preceding two and so interconnected as to yield appropriate responses to ordinary recurring stimuli; and (4) infiltrating these mechanisms of stimulus-response type, a differ- [Begin Page: Page 67] FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL 67 ent sort of adjusting apparatus which insures general integration of these systems, with provision for conditioning of reflexes and other forms of individually acquired behavior and for release of accumulated reserves of nervous potential as needed. These four groups intergrade but, in general, are recognizable. The peripheral fibers are grouped in functional systems, each of which is defined as comprising all nerve fibers and related endorgans, which are so arranged as to respond to excitation in a common mode, either sensory or motor. These functional systems are convenient anatomical units also, for all fibers of each sensory system, regardless of variations in the peripheral distribution of their end-organs and regardless of the particular nerve trunks or roots through which they connect with the brain, are segregated internally and converge into local areas or zones. In higher vertebrates (but less so in lower) the secondary connections of these terminal stations tend to retain their physiological specificity. From this it follows that the peripheral systems of sensory analyzers are extended into the brain as far as related central pathways are separately localized — in the human brain it may be even up to the projection areas of the cerebral cortex. Accordingly, we include in the sensory zone as here defined not only the terminal nuclei of peripheral sensory nerves but also their related nervous connections, so far as these are with other parts of the sensory zone and not directly with the motor zone. The neuromotor apparatus can be similarly analyzed into functional systems, each of which is concerned with the synergic activation of some particular group of muscles. This anatomical segregation of the functional systems is not carried to perfection, even in the human nervous system. The various modalities of cutaneous and deep sensibility, for instance, are not completely segregated and localized either peripherally or centrally. Yet this differentiation has gone so far that it provides our most useful guide in the analysis of the structure of the brain. The activities of the body may be divided into two major groups; (1) those concerned with adjustment to environment, the somatic functions, and (2) those concerned with the maintenance and reproduction of the body itself, visceral functions. These, of course, are not independent of each other; nutrition, for instance, involves somatic activity in the search and capture of food and visceral activity in its digestion and assimilation. Nonetheless, these types of function are so different, especially in the responses evoked, that this strictly [Begin Page: Page 68] 68 THE BRAIN OF THE TIGER SALAMANDER physiological criterion marks also the most fundamental structural analysis of the nervous system. Anatomically, the somatic systems of peripheral organs and nerves and central adjustors, including the proprioceptors, are, in general, rather sharply distinguished from the visceral. The systems are cross-connected by internuclear tracts, and some sensory systems, like the olfactory, may serve, on occasion, either somatic or visceral adjustments. A phylogenetic survey of these systems reveals remarkable plasticity in their interrelationships. Thus, taste buds, which in most vertebrates are typical interoceptors, may in some fishes be spread over the external surface of the body, where they serve exteroceptive functions, with corresponding changes in the anatomical pattern of the central apparatus of adjustment (chap, x; '446). On the motor side the apparatus of feeding and respiration exhibits still more remarkable transformations. In fishes this musculature is connected with the visceral skeleton — jaws, hyoid, and gill arches — and the functions performed are obviously visceral, though the larger part of this musculature is striated. The related parts of the nervous system are classified as special visceral motor. With suppression of the gills in higher animals, some of these muscles undergo remarkable transformations. Those which are elaborated to form the mimetic facial musculature of mammals become physiologically somatic ('22, '43). The classification of peripheral end-organs and their related nerves which has proved most useful grew out of the analysis of these nerves into their functional components, to which reference has just been made, by histological methods. Serial sections through the entire bodies of small vertebrates differentially stained for nerve fibers enable the investigator to reconstruct not only the courses of the nerves but also the arrangement of the functional systems represented in each of them and to follow these components to their peripheral and central terminals, a result that cannot be achieved by ever so skilful dissection. The first successful application of this method was Strong's analysis of the nerve components of the tadpole of the frog in 1895, a fundamental research which provided the generalized pattern which prevails, with endless modifications of details, throughout the vertebrate series, as has been abundantly demonstrated by numerous subsequent studies by many workers. This was followed in 1899 by my Doctor's dissertation on the nerve components of the highly specialized teleost, Menidia. From these [Begin Page: Page 69] FUNCTIONAL ANALYSIS, CENTRAL AND PERIPHERAL G9 and subsequent studies the peripheral nervous system of the head was analyzed into functional systems as follows: 1. Somatic sensory fibers of two groups. — (1) Exteroceptive systems, including (a) the specialized olfactory (in part), optic, auditory, and lateral-line nerves with differentiated end-organs, and (6) the nerves of general cutaneous and deep sensibility with simple free endings, these entering chiefly in the V nerve root with some in the VII, IX, and X roots. (2) Proprioceptive fibers from specialized endorgans of the internal ear and (probabljO lateral-line organs and also fibers from muscles, tendons, and other deep tissues. Here belongs also the peculiar mesencephalic root of the V nerve. See chapter x for further comments on the proprioceptive system. 2. Visceral sensory fibers of two types. — (1) With specialized endorgans, viz., the olfactory organ (in part) and the taste buds, the latter entering by the VII, IX, and X nerve roots. (2) Fibers of general visceral sensibility with free endings, entering in the same roots as the preceding and mingled with them. 3. Somatic motor fibers. — Somatic motor fibers which supply striated muscles derived from the embryonic somites, those in Amblystoma being limited to the nerves of the extrinsic muscles of the eyeball in the III, IV, and VI nerves. 4. Visceral efferent fibers of two types. — (1) Special visceral motor fibers of cranial nerves supplying striated muscles, not of somitic origin, related with the visceral skeleton, jaws, hyoid, branchial arches, and their drivatives (in the V, VII, IX, and X roots). (2) Preganglionic fibers of the general visceral (autonomic) system, terminating in sympathetic and parasympathetic ganglia, where they activate postganglionic fibers distributed to unstriated and cardiac muscles and glands (in the III, VII, IX, and X roots). The last system is not further considered in this work. For application of this analysis to the human nervous system see my Introduction to Neurology ('31a, chaps, v and ix). This analysis has yielded our most useful clues for resolution of the complexity of both peripheral nerves and brain. Descriptions of the peripheral end-organs and the courses of the nerves do not lie within the scope of this work. Some of these details which are significant for understanding their central connections are included in chapter x. [Begin Page: Page 70] CHAPTER VI PHYSIOLOGICAL INTERPRETATIONS APPARATUS OF ANALYSIS AND SYNTHESIS IN A primitive brain like that of Amblystoma the stable framework of localized centers and tracts performs functions that are primarily analytic. The sense organs are analyzers, each attuned to respond to some particular kind of energy. The sensory systems of peripheral nerves and the related internal sensory tracts are parts of the analytic apparatus, in so far as their functional continuity with the peripheral organs of the several modalities of sense can be traced. On the motor side similar conditions prevail. The neuromotor apparatus is organized in functional systems, each of which is adapted to call forth the appropriate sequence of action in a particular group of synergic muscles. These units are as truly analyzers as are those of the sensory systems, though in an inverse sense. Out of the total repertoire of possible movements, those, and only those, are selected which give the appropriate action. The efferent fibers are grouped, the members of each group being so bound together by central internuclear connections that they act as a functional unit adapted for the execution of some particular component of behavior, such as locomotion, conjugate movements of the eyeballs, seizing and swallowing food, and so on. The several sensory systems are so interconnected within the sensory zone as to react mutually with one another. They form a dynamic system so organized that all discharges from this zone are resultants of this interaction. This interplay has pattern. The various modalities of sense are not discharged into a single common pool of equipotential tissue. The sensory components of the nerves are segregated, more or less completely, so that related systems converge into dominant centers of adjustment— exteroceptors in the tectum, proprioceptors in the cerebellum, olfacto-visceral systems in the hypothalamus, olfacto-somatic systems in the habenula, and so on. A review of the internal architecture of the adult brain of Amblystoma suggests that the specifications of the general plan are drawn 70 [Begin Page: Page 71] PHYSIOLOCilCAL INTERPREIATIONS 71 in terms of current action. The elaboration of the analytic apparatus on the sensory side is carried only so far as is requisite to facilitate responses to any combination of sensory stimuli in patterns determined by the appropriate use of such motor equipment as the animal possesses. In species with simpler action systems the central analytic apparatus is less elaborate; in species endowed with more complicated motor organs the central architecture is more elaborate. In all species the peripheral sensory equipment determines the architectural plan of the primary centers of the sensory zone; internally of this level the details of the plan are shaped by two additional factors : first, the motor equipment available and, second, the amount and quality of the apparatus of correlation and integration required for the most efficient use of such sensory excitations as the animal experiences. The cross-connections between the sensory and motor zones are quite direct and simple in early embryological stages, so arranged as to provide uniform stereotyped responses to oft recurring situations. But as development advances these connections become more and more complicated, an intermediate apparatus of correlation is interpolated, and, correlated with this, the behavior becomes more diversified and unpredictable. In the sequence of development of behavior patterns this change can be accurately dated. For instance, in Amblystoma between the early swimming and early feeding stages, at about Harrison's stage 40, the swimming movements, which in younger stages are perfectly co-ordinated by the bulbo-spinal central apparatus alone, lose this autonomy, and participation of the midbrain is essential for the maintenance of efficient swimming, as was mentioned on page 62 in describing experiments by Detwiler ('45, '46). It is during this period that tecto-bulbar and tecto-spinal connections of essentially adult pattern are established ('39, p. 112). In human fetal development there is a similar critical period at about 14 weeks of menstrual age (Hooker, '44, p. 29). At this time the upper levels of the cerebrum acquire functional connections with the lower brain stem, and the behavior shows a corresponding change. "The fetus is no longer marionette-like or mechanical in the character of its movements, which are now graceful and fluid, as they are in the new-born." Synthesis and integration may be effected in various ways. The most evident nervous structures employed here are the internuclear tracts which form a complicated web of conductors, which interconnect the analytic units with one another so that the entire com- [Begin Page: Page 72] 72 THE BRAIN OF THE TIGER SALAMANDER plex forms an integrated equilibrated system. This is the apparatus of the stable heritable components of the action system — the reflexes and instincts. A second integrating apparatus is found in the allpervasive neuropil, and a third in specialized derivatives of the latter, the associational tissues locally differentiated in the brain stem and reaching maximal development in the cerebral cortex. The total behavior of neuromuscular type emerged within a preexisting bodily organization, which maintained the unity of the individual by nonnervous apparatus. The nervous system is from its first appearance a totalizing apparatus. Local differentiations of tissue for the analysis of sensory experience and of motor responses arise within this integrated structure, and local reflexes similarly emerged within a total neuromuscular pattern of action adapted to maintain the unity of the organization. As development advanced, the mechanisms of the local reflexes acquired increasing autonomy, but they are never completely emancipated from some control in the interest of the behavior of the body as a whole. The organic unity of the whole is preserved while local specificity is in process of development, and this unitary control is never lost during the normal life of the individual. THE STIMULUS-EESPONSE FORMULA The stimulus-response formula has wide application and great usefulness as a basic concept in physiology and psychology, but its apparent simplicity is illusory and has tended to divert attention from essential features of even the simplest patterns of behavior. This I have illustrated ('44a) by an examination of the simplest reflex connection known in Amblystoma — from retina to ocular muscles by way of the basal optic tract. The late G. E. Coghill, during a productive period of foi'ty years, studied the development of the action system of Amblystoma and the correlated processes of bodily growth. These researches have demonstrated beyond question that in this animal the neuromuscular system is so organized in prefunctional stages that, when first activated from the sensory zone, the resulting movement is a total response of all the musculature that is mature enough to respond to nervous excitation. These "total patterns" of activity are not disorderly, and they become progressively more complicated while the apparatus of local reflexes ("partial patterns") is slowly differentiated within the larger frame of the total pattern. The development of both the total pattern and the partial patterns is initiated cen- [Begin Page: Page 73] PHYSIOLOGICAL INTERPRETATIONS 73 trally, and throughout Hfe all of them are under some measure of unified central control so that the body acts as an integrated whole with diverse specialization of its parts (Coghill, '29; Herrick, '29). Coghill's contributions of factual observations and the principles derived from them have been critically reviewed by the writer in a book ('48), to which the reader is referred. The patterning of these orderly movements is determined by the intrinsic structure of the nervous system. This structural pattern is not built up during early development under the influence of sensory excitations, for in the embryo the motor and sensory systems attain functional capacity independently of each other; and when central connection between the sensory zone and the motor zone is made, the first motor responses to excitation exhibit an orderly sequence, the pattern of which is predetermined by the inherited organization then matured (Coghill '29, p. 87; '30, Paper IX, p. 345; '31, Paper X, pp. 158, 166). This early structural differentiation goes on independently of any stimulus-response type of activity, though the latter may modify the pattern of subsequent development. This is a principle of wide import, applicable not only in lower vertebrates but in higher forms as well (Coghill, '40), including man (Hooker, '44). The stimulus-response mechanism is not a primary factor in embryogenesis; it is a secondary acquisition. REFLEX AND INHIBITION It has been pointed out that the functions of the sensory and motor zones are fundamentally analytic — analysis of environmental influences and analysis of performance in adjustment to those influences. How the units of the analytic apparatus are actually related so as to insure the appropriate correlated action of the separate parts is the key problem, which must be resolved before animal (and human) behavior can be approached scientifically in other than a descriptive way. Good progress has been registered. The sensory and motor analytic apparatus has been exhaustively studied and well described; and this was the appropriate place to begin, for these organs are most accessible to observation and experiment. Because these systems of peripheral end-organs and the related pathways of conduction and centers of control are, in the human nervous system, obviously interconnected in stable and definitely localized patterns, it was natural to use this structural framework as the point of departure in the elaboration of the hypothetical superstructure of current doctrines of [Begin Page: Page 74] 74 THE BRAIN OF THE TIGER SALAMANDER reflexology. But reflexes can be conditioned, and this name for a well-known physiological fact is for the neurologist scarcely more than a symbol of complete ignorance of the mechanisms actually employed. The several reflexes have been so closely colligated with specific details of central architecture that the reflex arc came to be regarded as the primary unit of nervous organization, and it was assumed that the increasing complexity of the upper levels of the brain in higher vertebrates has been brought about by progressively more intricate interconnections among these elementary units. The integrative action of the nervous system was conceived in terms of the definition of mathematical integration — "the making up or composition of a whole by adding together or combining the separate parts or elements." This conception leaves unexplained how any additive process of this sort can result in such a unique centrally controlled unitary organization as we actually observe, capable of conditioning the reflexes in terms of individual experience (learning), of abstracting some common features of mixed experience and synthesizing these into quite original patterns of response, and of maintaining some measure of "spontaneous" or self-determined directive control. A far more serious charge against traditional doctrines of reflexology is the observed fact that in the development of Ambly stoma the early responses to external stimulation are not local reflexes but total movements of the entire available musculature. The integrated total pattern precedes in time the appearance of the partial patterns. These are individuated within the total pattern; they are integral parts of it, and for an appreciable time they are subordinate to it. Even in the adult animal the local partial patterns are not completely emancipated from control by the body as a whole. It is, indeed, impossible to find in this brain any sharply defined, well-insulated reflex arcs. What happens during the emergence of specific reflexes from the total reactions is, first, the development of an increasing number of collateral branches of the primary axons and the central linkage of sensory and motor pathways in ever more complicated patterns. Then, second, in the adjusting centers additional neurons are differentiated, the axons of which take longer or shorter courses, branching freely and participating in the formation of a nervous feltwork of extraordinary complexity. These neurons are not concerned primarily with specific reflexes but with the co-ordination and Integra[ Begin Page: Page 75] PHYSIOLOGICAL INTERPRETATIONS 75 tion of all movements. Some parts of this intricate fabric, generally witli thicker fibers, more or less well fasciculated, activate mass movements of primitive type, and other parts control local reflexes as these are individuated. But these systems of fibers are not segregated in comjjletely insulated reflex arcs. They are interconnected by collateral branches with one another and with the interstitial neuropil. There are lines of preferential discharge, but whether any one of them is actually fired depends on numberless factors of peripheral stimulation and central excitatory state. The phylogenetic history is parallel. The further down we go toward the primitive ancestral vertebrates, the less clear evidence do we find of definitely localized reflex arcs, and the overt behavior tends more toward mass movements of total-pattern type. It must be borne in mind that the development of the individual does not exactly recapitulate the phylogenetic development (Hooker, '44, pp. 15, 33). The pattern of the sequence of structural changes' which take place during prefunctional stages of growth is determined by the organization of the germ plasm and the interaction of the genetic factors with one another. This organization, in turn, has been determined during preceding evolutionary history in adaptation to the environment and habitus of the species in question. In broad lines the history of ancestral development is repeated in the growth of the embryo, but cenogenetic modifications of it may appear in adaptation to changing conditions, as illustrated, for instance, by the appearance of some local reflexes earlier in mammals than in amphibians. The structural organization of the brain sets off in sharp relief a few important general physiological principles. First, it is to be noted that the "resting" nervous system is not inert. The body acts before it reacts. There is always some spontaneous — that is, centrally excited — activity, and the importance of this factor increases as we ascend the phylogenetic scale. There is always intrinsic activity, as demonstrated, for instance, by the Berger rhythms, and it is always acted upon by numberless extrinsic agencies. When an excitation is received from the periphery, there results a change in the central excitatory state both locally and diffusely, which involves both activation and inhibition. Another general principle may be mentioned here. The flow of nervous impulses from receptor to effector is not one-way traflSc. [Begin Page: Page 76] 76 THE BRAIN OF THE TIGER SALAMANDER The excitation of a peripheral sense organ may be followed by an efferent discharge back to the receptor. An instructive illustration of this is seen in the auditory apparatus of mammals. Excitation of the cochlea is followed by an efferent return to the tensor tympani and stapedius muscles and also to the cochlea itself (the latter pathway recently demonstrated by Rasmussen, '46). Almost all contracting muscles report back to the center by a system of proprioceptive fibers. The central nervous system is full of similar reciprocating systems. Many of the fasciculated tracts of Ambly stoma are two-way conductors, transmitting in both directions, and there are numberless illustrations of a circular type of connection, efferent fibers of one center activating another, which has a return path, perhaps by a devious route, back to the first center. A neuropil may be interpolated in any of these types of circuit. The thalamo-cortical connections of the human brain are of this sort, exhibiting what Campion and Elliot Smith ('34) have aptly named a "thalamo-cortical circulation," a circulation not of blood but of nervous transmission. All parts of the cerebral hemispheres are in similar reciprocal interconnection, as has recently been emphasized and illustrated by Papez ('44). Here reference may be made to Dewey's ('96) stimulating analysis of the reflex-arc concept or, as he prefers to say, the "organic circuit" concept. This he elaborated in terms of psychology, and nearly twenty years later I made this comment about it ('13«) : "Let us see how it may be applied to biological behavior. The simple reflex is commonly regarded as a causal sequence: given the gun (a physiologically adaptive structure), load the gun (the constructive metabolic process), aim, pull the trigger (application of the stimulus), discharge the projectile (physiological response), hit the mark (satisfaction of the organic need). All of the factors may be related as members of a simple mechanical causal sequence except the aim. For this in our illustration a glance backward is necessary. An adaptive simple reflex is adaptive because of a pre-established series of functional sequences which have been biologically determined by natural selection or some other evolutionary process. This gives the reaction a definite aim or objective purpose. In short, the aim, like the gun, is provided by biological evolution and the whole process is implicit in the structurefunction organization which is characteristic of the species and whose nature and origin we need not here further inquire into The aim (biological purpose) is so inwrought into the course of the process that it cannot be dissociated. Each step is an integral part of a unitary adaptive process to serve a definite biological end, and the animal's motor acts are not satisfying to him unless they follow this predetermined sequence, though he himself may have no clear idea of the aim. These reactions are typically organic circuits Always the process is not a simple sequence of distinct elements, but rather a series of reactions, each of which is shaped by the interactions of external stimuli and a preformed or innate structure which [Begin Page: Page 77] PHYSIOLOGICAL INTERPRETATIONS 77 has been adapted by biological factors to modify the response to the stimuH in accordance with a purpose, which from the standpoint of an outside observer is teleological, i.e., adapted to conserve the welfare of the species." This apparent teleology is commented upon in chapter viii. Since the passage just quoted was written, control of gunfire by radar has been perfected, thus reinforcing our analogy at one weak spot. In the reflex the "aim" does not precede the stimulus that pulls the trigger; it is automatically adjusted to the stimulus as in radar. But this automatism in both cases is dependent upon the presence of a preformed structure adapted to provide it. Our analysis of the adult structure of the brain of Amblystoma confirms and supplements the conclusions reached by Coghill from his study of the development of the same species. His major contribution, as I see it, was the demonstration of the primacy of the integrative factors in the development of behavior patterns and of some of the features of structural growth during the individuation of local partial patterns within the larger total pattern. The adult structure of the brain of Amblystoma is in perfect conformity with the conclusions to which he was led. One of these conclusions should receive special emphasis here, for it clarifies our conception of what the reflex is in general, and in particular it helps us over some hard places in our attempt to discover the actual mechanisms involved in the individuation of local reflex patterns within the frame of the total pattern. In the central resolution of forces which eventuates in some particular pattern of overt movement there is always an inhibitory factor (Coghill, '36, '43). In discussing the individuation of partial patterns (local reflexes) from the total pattern, he wrote ('40, p. 45): "Individuation is obviously the result of organized inhibition The major division of the total pattern must be under inhibition when a part acquires independence of action, and the same part can be inhibited while the major segment of the total pattern acts. So that the whole individual probably acts in every response, either in an excitatory or inhibitor}^ way," This he generalized in the following statement ('30, p. 639): "For an appreciable period before a particular receptor field acquires specificity in relation to an appropriate local reflex its stimulation inhibits the total reaction. Inhibition, accordingly, through stimulation of the exteroceptive field, begins as a total pattern. It is then in a field of total inhibition that the local reflex emerges. The reflex may, therefore, be regarded as a total behavior pattern which consists of [Begin Page: Page 78] 78 THE BRAIN OF THE TIGER SALAMANDER two components, one overt or excitatory, the other covert or inhibitory. The essential anatomical basis for this is (1) in the mechanism of the total pattern of action, or primary motor system, and (2) in the mechanism of the local reflex, or secondary motor system; the mechanism of the total pattern being inhibited and that of the reflex excited. But since inhibition is not a static condition but a mode of action, the mechanism of the total pattern must be regarded as participating in every local reflex." This conception of the reflex as involving a factor of inhibition of the total pattern Hnked with excitation of the partial pattern is fruitful. Total inhibition plays a more obvious role in the overt behavior of amphibians than in most other animals, not only in embryogenesis of behavior but also in the adult. This was emphasized by Whitman ('99) in his classic description of the behavior of Necturus. In my manuscript notes of a conference with Dr. Coghill on January 1, 1929, I find a record of his remarks which is here transcribed. "The first neurons to differentiate in Amljlystoma are in the floor-plate. These and others adjacent form the primary motor column, the dominant function of which is activation of muscles of the same side for mass movement of the trunk and limbs and inhibition of the musculature of the opposite side which is in the same phase of locomotor movement. In later stages, when mechanisms of specific local reflexes emerge, residual neurons in the region of the floorplate maintain their functional importance for mass movements as activators of the whole somatic motor apparatus. They may prime this neuromotor system, putting it into a subliminal excitatory state in advance of its patterned activation. "At an age which immediately precedes the first feeding reactions and before it is possible to open the mouth and swallow, the larva will react to a moving object in front of the eyes by a total reaction, a leap forward. It cannot seize the object. The general activator mechanism here comes to overt expression before the specific local reflex patterns are mature enough to function. After feeding activities have matured there is a similar general activation, accompanied by inhibition, as illustrated by the 'regarding' reaction [p. 38]. A larva which had been feeding for several days was stimulated by moving a hair slowly across the field of vision. The animal responded by moving the head slowly following the hair. The head is bent to the side, with rotation of the eyes, movement of the fore limbs, and adduction of both hind limbs. When the hair was not too far distant, the animal finally, at the end of this 'regarding' reaction, jumped after it. Here there is a clear distinction between what Sherrington calls the anticipatory phase and the consummatory phase of the reaction, and evidently in the anticipatory phase inhibition plays the major role. This is obvious also in almost all adult behavior of these animals." The mechanism of central inhibition is still obscure. There is some evidence that a nervous impulse impinging upon a central neuron may, on occasion, activate the element, or under other conditions of central excitatory state, strength, or timing of the afferent flow it may inhibit activity ui process. Whether or not this is true, it is well known that a central neuron may exhibit a large variety of types of [Begin Page: Page 79] niYSIOLOGICAL INTERPKETA'l IONS 79 synaptic junctions, differing in histological structure, electrical properties, and perhaps also in chemical reactivity. These afferent fibers may come from widely separated regions with diverse functions, and the impulses delivered may differ in intensity and temporal rhythm. Bodian's description ('37, '4'2) of axon endings on Mauthner's cell of the medulla oblongata shows four main types of synaptic contact which vary from 0.5 to 7/i in extent, with a wide variety of arrangements. There are between four and five hundred of these endings on a single cell, and the presumption is legitimate that these diverse structures are correlated with significant differences in electrical and chemical properties, including the timing of the pulses of transmission. It has been suggested that some of the influences transmitted across the synaptic junctions are excitatory and that others are inhibitory. Synaptic junctions on dendrites are in some cases structurally different from those on the axon hillock or axon, and they may be activated from different sources. Some observers believe that excitation of dendrites is excitatory and of axons is inhibitory, a supposition supported with physiological evidence by Gesell and Hansen ('45, p. 156). In their theory of the electronic mechanism of activation and inhibition, these functions are viewed as basically similar, activation being associated with an increasing, and inhibition with a decreasing, intensity of the electronic current. The connections of horizontal cells of the retina as described by Polyak ('41, p. 385) suggest to him a different inhibitory apparatus. The horizontal cells may exert an inhibitory influence upon the synapses between the rods and cones and the bipolar cells, that is, the synapses of the horizontal cells may function as "countersynapses" to the photoreceptor- bipolar synapses. Whatever may be the mechanism employed in central inhibition, it is clear that in some parts of the brain excitatory functions predominate, in other parts inhibitory functions. Noteworthy examples of the latter are (1) the head of the caudate nucleus (Fulton, '43, p. 456) ; (2) a region in the reticular formation of the medulla oblongata explored by Magoun ('44) ; and (3) certain specific zones of the cerebral cortex (areas 4^, ^s, 19s, and some others) which are known as "suppressor bands." In all these cases, excitatory and inhibitory fields are intimately related physiologically in such a way as to secure appropriate balance of activation and inhibition of the members of synergic systems of muscles in proper sequence. The role of general inhibition in the patterning of behavior has [Begin Page: Page 80] 80 THE BRAIN OF THE TIGER SALAMANDER been under investigation for several years by Beritoff and his colleagues. The first half of the fifth volume of the Transactions of his institute is devoted to studies on the nature of general inhibition and its role in the co-ordination of cortical activity and reflex reactions of the spinal cord. Beritoff believes that the neuropil possesses an inhibitory function — slow changes in voltage, expressing the active state of the neuropil, show an anelectrotonic effect on the cellular bodies, lowering excitability in them and weakening the excitation. The evidence is drawn from both somatic and visceral stimulation. He writes ('43, p. 142) : "Thus, during each reflex reaction in the visceral organs, taking place in response to a stimulation of the interoceptors and of visceral afferent fibers, just exactly as during somatic reflexes, the spinal cord acts as a whole, making the given reflex local and every spinal reflex reaction entire by means of general inhibition." This is essentially the same as Coghill's position as stated in the preceding quotations. In other articles in the same volume the role of the neuropil in a great variety of spontaneous and stimulated activities of the brain is emphasized by Beritoff. The neuropil as a whole is not, in my view, a specific inhibitor. It may partipciate on occasion in either excitation or inhibition, and in the inhibitory phase it acts as part of the covert component of the reflex or of mass action, as the case may be, in Coghill's analysis as quoted above. In my discussion of the habenular system (chap, xviii) and the interpeduncular nucleus (chap, xiv) I have ventured to suggest a possible mechanism through which general inhibition effected in the interpeduncular neuropil may operate in the facilitation of both mass movement and local reflexes. On this hypothesis this local band of neuropil must be able to act as a specific inhibitor in Beritoff's sense. The amphibian neuropil in its various forms . is structurally adapted for a considerable variety of functions of different grades of specialization. There is generally a diffuse spread of terminals, so that a single incoming fiber may activate many neurons of the second order. If the receptive tissue is homogeneous, this provides for simple central summation. If the receptive tissue is heterogeneous, as in most sensoiy fields, this arrangement facilitates mass movement of the musculature or total patterns of action. If many fibers converge upon a single neuron, the threshold of central excitation is lowered, as in the mitral cells of the olfactory bulb and in the *'motor pool," [Begin Page: Page 81] PHYSIOLOGICAL INTERPRETATIONS 81 as this concept has been developed by Sherrington. If the activated motor pool is large, with wide distribution of the efferent fibers, complicated integrated mass movement may result. If the pool is small, with a single final common path, a local reflex may follow. If the outlet comprises a number of open channels with different connections and physiological properties, there is provision for discriminative response, the selection being made (presumably) in terms of the central excitatory state of the components of the system ('42, p. 295). It has been objected that the preceding comments on the limitations of current doctrines of reflexology are based upon the amphibian organization, which is aberrant and degenerate and therefore not typical or significant in the interpretation of the behavior of higher animals. But, even so, the Amphibia live well-ordered lives, and their behavior conforms in basic patterns with that of other vertebrates. We want to know how they behave as they do. Accepting the current view that Amblystoma is a retrograde descendant of some more highly specialized ancestor now extinct and that some of its characters are aberrant, yet the evidence seems to me adequate that such retrogression as may have occurred has been toward a generalized form ancestral to modern amphibians and mammals. Conclusion. — I have assembled in these pages some factual description of observed structure, together with speculative interpretations of its probable physiological significance. The organic structure here under consideration is not something vague and ill-defined. Its anatomical distribution, histological organization, and fibrous connections can be described with precision. Not until this has been done can our imperfect knowledge of its functions be advanced by experiments designed to reveal its physiological properties. In a discussion of "localized functions and integrating functions" more than a decade ago ('34a), the significance of neuropil in the evolution of cerebral structure was summarized in these words : "The neuropil is the mother tissue from which liave been derived both the specialized centers and tracts which execute the refined movements of the local reflexes and the more general web which binds these local activities together and integrates the behavior. It retains something of embryonic plasticity and so is available as a source of raw material for two very dift'erent lines of specialization — first, toward the structural heterogeneity requisite for the execution of localized reflex and associational functions, and, second, toward the more generalized and dispersed apparatus of total or organismic functions of tonicity, summation, reinforcement, facilitation, inhibition, 'spontaneity,' constitutional disposition and temperament, and extra-reflex activities in general." [Begin Page: Page 82] 82 THE BRAIN OF THE TIGER SALAMANDER PRINCIPLES OF LOCALIZATION OF FUNCTION The gi-eat advances that have been made in the diagnosis and treatment of nervous diseases have been due in large measure to the more accurate mapping of the structural features of the nervous system and recognition of the specific functions of its several parts. Before a disorder can be successfully treated we must know what it is and where it is. The most notable triumphs in this medical field have been registered with those diseases whose situs can be recognized and then subjected to appropriate therapy or surgery. Even a systemic disorder like anemia has localization in blood corpuscles and blood-forming organs; and a general infection, like poliomyelitis, spreads in preferential paths determined by the histochemical structure of the tissue. The stable heritable tissues of the nervous system are most accessible to this kind of inquiry, of diagnosis, and of treatment; conquest of the unlocalized disorders has been retarded. Some kinds of disorder, particularly those of primary concern to psychiatrists, have resisted all attempts at localization in accordance with conventional principles, and in the field of physiology the concept of local reflex arcs has limited application. The various attempts to elaborate a comprehensive account of animal and human behavior in terms of conventional reflexology have broken down. These conspicuous failures have led some competent authorities to question the over-all significance of localization in space of nervous functions and to search for other principles in the realm of pure dynamics or chemical interaction or some as yet unknown factors which operate quite independently of stable structural patterns. But no nervous tissue is structurally homogeneous or physiologically equipotential. In this connection it is interesting to note that Lashley, the leading advocate of the equipotentiality of the nervous tissues, has given us clear demonstration of point-to-point projection of retinal loci upon the lateral geniculate body and the cerebral cortex of the rat (Lashley, '34, '34a). This is the most refined anatomical localization of function known. In a later communication ('41) he demonstrated a very precise projection of the thalamic nuclei upon the cerebral cortex and added: "A functional interpretation of the spatial arrangement of the thalamo-cortical connections is not justified on anatomic grounds alone for any sensory system." Somewhere between the extreme views of rigid localization in spatial patterns and a labile physiological equipotentiality a practicable working conception of the meaning of the structural configuration |