Lamprey Neurotransmitters

Cross references:   Subcortical Brain    Lamprey Acetylcholine   
Lamprey Dopamine     Lamprey GABA     Lamprey Glutamate       
Lamprey Serotonin     Amphioxus Neurotransmitters      
Salamander Neurotransmitters    

Searching for "lamprey neurotransmitters" yielded:         
        PubMed = 480      
        Google = 851,000  

Effects of iontophoretically applied drugs on spinal interneurons of the lamprey.   
from the Abstract
    1. Intracellular records were obtained from giant interneurones in the isolated spinal cord of the sea lamprey. The cells had a mean resting potential of about 75 mV and action potentials with overshoots of about 35 mV. Their input resistances, measured by passing polarizing currents through the recording pipette, were in the range 3-7 MOmega. 
    2. Iontophoretic ejection of gamma-aminobutyric acid (GABA) from a micropipette placed near the surface of a cell resulted in a slight hyperpolarization, accompanied by a marked reduction in input resistance. The reversal point for the potential change was about 5 mV greater than the resting membrane potential. 
    3. Iontophoretic application of L-glutamate to the cells produced a depolarization with a decrease in input resistance much smaller than that accompanying a GABA potential of similar amplitude. The action potential amplitude was reduced by L-glutamate application. The reversal potential could not be determined accurately but appeared to be near zero membrane potential. 
    4. Glutamate application produced, in addition, a burst of inhibitory synaptic potentials in the cell, presumably by depolarizing either inhibitory presynaptic nerve terminals or nearby inhibitory cell bodies. 
    5. Acetylcholine (ACh) produced no detectable change in membrane resistance or potential. 
    6. Application of the three drugs to first-order sensory cells in the spinal cord had no effect on their membrane properties." 
    172 Related citations:    
     15 Cited by's:    
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Inhibitory conductance changes at synapses in the lamprey brainstem
    "Although the conductance and kinetic behavior of inhibitory synaptic channels have been studied in a number of nerve and muscle cells, there has been little if any detailed study of such channels at synapses in the vertebrate central nervous system or of the relation of such channels to natural synaptic events. In the experiments reported here, current noise measurements were used to obtain such information at synapses on Müller cells in the lamprey brainstem. Application of glycine to the cells activated synaptic channels with large conductances and relaxation time constants (70 picosiemens and 33 milliseconds, respectively, at 3 degrees to 10 degrees C). Spontaneous inhibitory synaptic currents had a mean conductance of 107 nanosiemens and decayed with the same time constant. In addition, the glycine responses and the spontaneous currents had the same reversal potential and both were abolished by strychnine. These results support the idea that glycine is the natural inhibitory transmitter at these synapses and suggest that one quantum of transmitter activates about 1500 elementary conductance channels."
glycine is the natural inhibitory transmitter at these synapses"  
    101 Related citations:
    and 2 Cited by's.

Effects of bath-applied excitatory amino acids and their analogs on spinal interneurons of the lamprey.     
    "Depolarizations, conductance increases and time courses of the responses to bath application of glutamate, aspartate, DL-homocysteate, N-methyl-DL-aspartate (NMDLA), quisqualate and kainate were determined in interneurons of the isolated spinal cord of the lamprey, one of the most primitive vertebrates. Conductance increases produced by these excitants in perfusate containing tetrodotoxin (0.5 microgram/ml), 4-aminopyridine (1 mM) and without Ca2+ were very small in comparison with those produced by glycine or GABA. NMDLA-induced depolarizations were associated with conductance decreases and rhythmic oscillations in membrane potentials in this perfusate. Quisqualate was strongest among these amino acids in producing depolarizations and conductance increases. Responses induced by analogs were slower than those produced by glutamate and aspartate. Phylogenetic distribution of N-methyl-D-aspartate receptors on neurons and muscles is discussed."    
     201 Related citations:    

Serotonin modulates the central pattern generator for locomotion in the isolated lamprey spinal cord.   
    "The central pattern generator for locomotion in the spinal cord of the lamprey can be activated in vitro by the addition of D-glutamate to the bathing saline. Serotonin has no effects when bath-applied alone, but it modulates the D-glutamate-activated swimming pattern. Three major effects are observed: a dose-dependent reduction in the frequency of rhythmic ventral root burst discharge; enhancement of the intensity of burst discharge, due in part to the recruitment of previously inactive motoneurones; prolongation of the intersegmental phase lag. Motoneurone activation appears to result from enhanced synaptic drive from the central pattern generator; no direct effects of serotonin on the motoneurones themselves (resting potential, input resistance or threshold for action potential generation) were observed. Theoretical and experimental studies suggest that the prolongation of the intersegmental phase lag results at least in part from differential effects of serotonin on segmental oscillators in different parts of the spinal cord. Isolated caudal pieces of the cord were more strongly affected by serotonin than isolated rostral pieces. We propose that serotonin may be an endogenous modulator of the central pattern generator for locomotion in the lamprey. It may have a role in the generation of a family of related undulatory movements (swimming, crawling, burrowing) by a single central pattern generator."   
My comment
    I'm confused.  This reference used D-glutamate to activate swimming patterns.  The previous two references used L-glutamate.    
     167 Related citations:    
     17 Cited by's:   
     Free full text    

Activation of NMDA receptors elicits fictive locomotion and bistable membrane properties in the lamprey spinal cord.   
    "The motor pattern underlying locomotion in the lamprey can be elicited in the spinal cord in vitro by applying excitatory amino acids that activate NMDA receptors. When this is done oscillatory membrane potentials phase-linked with the locomotory rhythm can be recorded in different types of neurones. In some spinal neurones large amplitude oscillation continues after elimination of synaptic input with application of TTX. This oscillatory pacemaker-like activity is dependent on an activation of NMDA receptors, and is probably important in the generation of locomotion."  
"The motor pattern underlying locomotion in the lamprey can be elicited in the spinal cord in vitro by applying excitatory amino acids that activate NMDA receptors."  
    See:  Central Pattern Generators  for partial Abstract

1985    286<349 
Immunohistochemical demonstration of some putative neurotransmitters in the lamprey spinal cord and spinal ganglia: 5-hydroxytryptamine-, tachykinin-, and neuropeptide-Y-immunoreactive neurons and fibers.
    Neurotransmitters:  5-HT, tachykinin, neuropeptide Y 

Excitatory synaptic drive for swimming mediated by amino acid receptors in the lamprey.  
    "These results suggest that a major part of the excitatory drive for swimming in lamprey motoneurons is generated by populations of propriospinal interneurons with relatively long descending and/or short ascending axons, which fire rhythmically during swimming and release an amino acid transmitter that excites motoneurons through N-methyl-D-aspartate (NMDA) and non-NMDA receptors."  
    Key point
amino acid transmitter that excites motoneurons ..."  
     222 Related citations:    
     5 Cited by's  
    - Free full text -                        

    Neurotransmitters:  5-HT 

Immunohistochemical and chromatographic studies of peptides with tachykinin-like immunoreactivity in the central nervous system of the lamprey. 


Efficiency of electrical transmission in reticulomotoneuronal synapses of lamprey spinal cord.   
Synaptic responses in motoneurons in the isolated spinal cord of the lamprey during stimulation of the reticulospinal axons were examined. Chemical transmission in the synapses was partially or completely blocked by temperature reduction of the perfusing solution, pentobarbitone application or substitution of Mn2+ ions for Ca2+ in the perfusate.
    Excitatory postsynaptic potentials (EPSPs) which were indifferent to the influences mentioned above, had an amplitude of 6-12 mV and were capable of evoking action potentials (APs) in motoneurons due to their high amplitude, the absence of a shunting effect at the postsynaptic membrane and the fast rise-time of the wave front.  
    The suggestion is made that the electrical transmission is involved in functioning of the lamprey nervous system. Its stability and efficiency are likely to ensure functional connection between the brain and spinal cord under such unfavourable conditions when the chemical transmission does not operate and when the ability for locomotion would be prerequisite for the individual to survive."      
My comment
    The last paragraph sounds a bit like  Lamprey Fast-Slow Twitch .     
    106 Related citations:  

Single sensory neurons activate excitatory amino acid receptors in the lamprey spinal cord.  
The effects of excitatory amino acid (EAA) antagonists were tested on sensory afferent excitation in the lamprey spinal cord. Paired intracellular recordings were made from mechanosensory neurons (dorsal cells) and second order sensory neurons (giant interneurons). Stimulation of individual dorsal cells evoked mono- and/or polysynaptic excitatory postsynaptic potentials (EPSPs) in giant interneurons. These EPSPs were depressed by the EAA antagonists cis-2,3-piperidine dicarboxylate and kynurenic acid.  
    Small components of the synaptic potentials were due to electrical coupling since they were not depressed by EAA antagonists or by calcium-free solution. The N-methyl-D-aspartate antagonist 2-amino-5-phosphonovalerate did not depress short-latency EPSPs. Thus, mechanosensory neurons in the lamprey spinal cord activate EAA receptors (kainate/quisqualate receptors) on interneurons, via mixed chemical and electrical synapses."   
My comment
    Once again I find myself wondering about the possible relationship between "electrical synapses" and  Lamprey Fast-Slow Twitch .     
    175 Related citations:   
See paper for individual links. 

Reticulospinal neurones activate excitatory amino acid receptors.   
Paired intracellular recordings were used to study the monosynaptic excitatory postsynaptic potentials (EPSP) in lamprey motoneurones evoked by stimulation of single reticulospinal Müller and Mauthner cells. The chemical component of the synaptic potentials was depressed by both application of the non-selective excitatory amino acid antagonists kynurenic acid and cis-2,3-piperidine dicarboxylate. The N-methyl-D-aspartate (NMDA) antagonists Mg2+ and 2-amino-5-phosphonovalerate caused a selective depression of a late component of the EPSP. Thus, fast-conducting reticulospinal neurones appear to release an excitatory amino acid acting at both NMDA and non-NMDA receptors."  
My comment
    I trust the "paired intracellular recordings", but I think that the "application of the non-selective excitatory amino acid antagonists" tested for neuromodulators rather than neurotransmitters. 
    and 10 Cited in's   

Survey of neuropeptide-like immunoreactivity in the lamprey spinal cord. 
The results suggest that the lamprey spinal cord has several fiber systems containing peptides sharing immunogenic properties with mammalian neuropeptides."    
    Neurotransmittersmammalian-like neuropeptide   

Newly identified 'glutamate interneurons' and their role in locomotion in the lamprey spinal cord. 
In the isolated spinal cord, these neurons act simultaneously with their postsynaptic motoneurons during fictive swimming. They are small and numerous, and they monosynaptically excite both motoneurons and inhibitory premotor interneurons. "  
    My comment
What is a "premotor interneuron?  Does it link sensory input to motor output? 
    Neurotransmitters:  glutamate 

1987    266<349  
N-methyl-D-aspartate receptor-induced, inherent oscillatory activity in neurons active during fictive locomotion in the lamprey.     
Free Article   
the results are compatible with an involvement of inherent, oscillatory membrane properties during fictive locomotion in the lamprey spinal cord."  
    My hypothesis
Although there is no specific mention of central pattern generators (CPGs), the patterns produced by CPGs would appear to be oscillations, and any oscillations would appear to produce patterns. 

Voltage clamp analysis of lamprey neurons--role of N-methyl-D-aspartate receptors in fictive locomotion. 
Voltage-clamped neurons observed during NMDA-induced fictive swimming show excitatory and inhibitory synaptic currents in phase with the ipsilateral and contralateral ventral root discharges, respectively."  
    Neurotransmitter:  NMDA 

Excitatory amino acid-evoked membrane currents and excitatory synaptic transmission in lamprey reticulospinal neurons.  
The characteristics of excitatory amino acid-evoked currents and of excitatory synaptic events have been examined in lamprey Müller neurons using voltage clamp and current clamp recording techniques. Application of glutamate evoked depolarizations associated with a decrease in input resistance."  
The order of potency of the excitatory amino acid agonists was quisqualate greater than kainate greater than glutamate greater than aspartate, while N-methyl-D-aspartic acid (NMDA) was inactive."  
It is concluded that both glutamate responses and excitatory synaptic transmission in lamprey Müller neurons are mediated by non-NMDA-type receptors and that these receptors are associated with ionic channels with a low elementary conductance. The combined pharmacological and biophysical characteristics of these responses are therefore different from those previously reported in other preparations. Spontaneous (but not stimulus-evoked) inhibitory synaptic events in Müller neurons were blocked reversibly by 1 mM KYN but not by 100 microM APV, suggesting that excitation of interneurons inhibitory to Müller cells was also mediated by non-NMDA receptors."   
My comment
    I think the experimental substances were bath-applied and therefore neuromodulators and not neurotransmitters.     
   889 Related citations

Possible target neurons of the reticulospinal cholecystokinin (CCK) projection to the lamprey spinal cord: immunohistochemistry combined with intracellular staining with lucifer yellow.  

A subpopulation of reticulospinal neurons in the posterior rhombencephalic reticular nucleus in lamprey contains a cholecystokinin (CCK)-like peptide."  
    Neurotransmitter:   cholecystokinin (CCK)-like peptide 

1988  256<349
Immunohistochemical studies of cholecystokininlike peptides and their relation to 5-HT, CGRP, and bombesin immunoreactivities in the brainstem and spinal cord of lampreys.

In the spinal cord, three separate systems reacted with CCK antisera."  
Neurotransmitters:  5-HT, bombesin, cholecystokinin (CCK)-like peptide 

The effect of an uptake inhibitor (dihydrokainate) on endogenous excitatory amino acids in the lamprey spinal cord as revealed by microdia

1989    244<349 
Identification of excitatory interneurons contributing to generation of locomotion in lamprey: structure, pharmacology, and function.  
    Discussion of "excitatory interneurons",  but nothing about specific neurotransmitters or receptors.

Further evidence for excitatory amino acid transmission in lamprey reticulospinal neurons: selective retrograde labeling with (3H)D-aspartate.   
The distribution of radiolabeled neurons in the brain stem of Lampetra fluviatilis was studied following unilateral injections of (3H)D-aspartate in the rostral spinal cord.  
    After survival periods of 1-3 days, labeled perikarya were present within and nearby the posterior, middle, and anterior rhombencephalic reticular nuclei and in the mesencephalic reticular nucleus.  
    The highest number of (3H)D-aspartate labeled cell bodies were present in the posterior rhombencephalic reticular nucleus. The labeled reticulospinal neurons were distributed mainly ipsilateral to the injection site and included the giant Müller cells as well as medium-sized and small neurons. Contralateral labeling occurred in cell bodies scattered along the lateral margin of the rhombencephalic reticular formation, the most rostral of these contralaterally projecting neurons being the Mauthner cell.  
    The (3H)D-aspartate labeling correlates with previous electrophysiological studies showing that lamprey reticulospinal neurons utilize excitatory amino acid transmission."  
    106 Related citations:   
"lamprey reticulospinal neurons utilize excitatory amino acid transmission."

1989   240<349
Monosynaptic excitatory amino acid transmission from the posterior rhombencephalic reticular nucleus to spinal neurons involved in the control of l...   
    See:  Reticulospinal Transmission  for full Abstract, Related citations and Cited by's.   

Three types of GABA-immunoreactive cells in the lamprey spinal cord. 
    Neurotransmitter:  Histamine 

1991   228<349
Presynaptic GABAA and GABAB Receptor-mediated Phasic Modulation in Axons of Spinal Motor Interneurons.   
    See:   GABA/Glycine Inhibition   for full Abstract, Related citations and Cited by's. 

Putative GABAergic input to axons of spinal interneurons and primary sensory neurons in the lamprey spinal cord as shown by intracellular Lucifer yellow and GABA immunohistochemistry. 
    See:  Lamprey GABA  for full Abstract, Related citations and Cited by's.   

1991    223<349 
5-Hydroxytryptamine depresses reticulospinal excitatory postsynaptic potentials in motoneurons of the lamprey.   
    Neurotransmitter:  5-HT   

Co-localized GABA and somatostatin use different ionic mechanisms to hyperpolarize target neurons in the lamprey spinal cord.
"gamma-Aminobutyric acid (GABA) and somatostatin are co-localized in cells close to the central canal in the lamprey. These cells project to the lateral margin of the spinal cord where they form a GABA and somatostatin containing plexus. Stretch receptor neurons (edge cells) are situated along the lateral margin of the spinal cord and their dendrites extend into the GABA and somatostatin containing plexus. To investigate whether GABA and/or somatostatin exert an affect on edge cells, these putative transmitters were applied from extracellular pipettes onto edge cells during intracellular recordings.  

    Both GABA and somatostatin hyperpolarized the edge cells but through different ionic mechanisms. GABA activated a chloride current while somatostatin activated a current most likely carried by potassium which, however, could not be blocked by any of the conventional potassium blockers."   
101 Related citations

Dorsal root and dorsal column mediated synaptic inputs to reticulospinal neurons in lampreys: involvement of glutamatergic, glycinergic, and GABAergic transmission.      

     "This study was aimed at characterizing the inputs from dorsal roots and dorsal columns to reticulospinal neurons within the posterior rhombencephalic reticular nucleus in the lamprey. The in vitro isolated brainstem and spinal cord preparation was used.  
    Microstimulation of dorsal roots and columns on both sides induced, in identified reticulospinal neurons, synaptic responses which consisted of large IPSPs mixed with excitation, particularly from stimulation on the ipsilateral side.  
    When the spinal cord was selectively exposed to kynurenic acid or to Ca2+ free Ringer's containing 2mM Mn2+, synaptic responses to stimulation of dorsal roots and columns were not modified, whereas the same responses were abolished when the brainstem was exposed selectively to kynurenic acid, thus suggesting that the responses were carried by long fibres ascending directly to the brainstem.  
    The excitatory and inhibitory synaptic responses are relayed by interneurons located in the brainstem. The ascending excitatory inputs to inhibitory interneurons and, most likely, also to excitatory interneurons, use excitatory amino acid transmission.  
    Inhibitory responses were abolished by adding the glycinergic antagonist strychnine (5 microM) to the physiological solution, thus suggesting that inhibitory interneurons use glycine transmission. The synaptic transmission was depressed by (-)-baclofen, a GABAB agonist, probably acting at a presynaptic site.  
    Taken together, the present results suggest that dorsal root and dorsal column stimulations give rise to disynaptic inhibition and excitation of reticulospinal neurons mediated by excitatory and inhibitory amino acid transmission via brainstem interneurons."  
    252 Related citations:   
No forwarding link.  See PubMed abstract.   

5-HT innervation of reticulospinal neurons and other brainstem structures in lamprey.  
In order to determine if reticulospinal neurons involved in the control of locomotion and responsive to exogenously applied 5-hydroxytryptamine (5-HT) are innervated by fibers that contain serotonin, the serotoninergic innervation of reticulospinal neurons, identified by retrograde labeling with fluorescein-conjugated dextran-amine (FDA), was investigated by immunohistochemistry in the lamprey brainstem.  
    A widespread distribution of 5-HT immunoreactive (5-HT-ir) fibers was seen within the basal plate of the brainstem, an area containing reticulospinal somata and dendritic aborizations. Numerous 5-HT varicose fibers were found in close relation to large reticulospinal cell bodies, particularly in the middle and anterior rhombencephalic reticular nuclei (MRRN and ARRN). Some of these reticulospinal somata were surrounded by a very dense pericellular 5-HT innervation. 5-HT-ir fibers were also seen in other brain structures that are known to influence reticulospinal neurons such as the rhombencephalic alar plate containing sensory relay interneurons, cranial nerves (III-X), cerebellum, and tectum.  
    These findings suggest that, as in the spinal cord, motor behavior controlled by reticulospinal neurons may be subject to a serotoninergic modulation." 
    149 Related citations:   

Neural networks that co-ordinate locomotion and body orientation in lamprey. 

   See:  Central Pattern Generators  for partial abstract

1995   172<349
Reticulospinal neurones provide monosynaptic glycinergic inhibition of spinal neurones in lamprey.  
glycine is the neurotransmitter of these inhibitory reticulospinal neurones."  


Trigeminal inputs to reticulospinal neurones in lampreys are mediated by excitatory and inhibitory amino acids.
    "Reticulospinal (RS) neurones integrate sensory inputs from several modalities to generate appropriate motor commands for maintaining body orientation and initiation of locomotion in lampreys. As in other vertebrates, trigeminal afferents convey sensory inputs from the head region.  
    The in vitro brainstem/spinal cord preparation of the lamprey was used for characterizing trigeminal inputs to RS neurones as well as the transmitter systems involved. The trigeminal nerve on each side was electrically stimulated and synaptic responses, which consisted of mixed excitation and inhibition, were recorded intracellularly in the middle and posterior rhombencephalic reticular nuclei.  
    The EPSPs were mediated by activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptors. An increase in the late phase of the excitatory response occurred when Mg2+ ions were removed from the Ringer's solution. This effect was antagonized by 2-amino-5-phosphonopentanoate (2-AP5) or reversed by restoring Mg2+ ions to the perfusate suggesting the activation of N-methyl-D-aspartate (NMDA) receptors.  
    IPSPs were mediated by glycine. These findings are similar to those reported for other types of sensory inputs conveyed to RS neurones, where excitatory and inhibitory amino acid transmission is also involved."   
    This reference starts out by describing electrical stimulation of a nerve and electrically monitoring the response, but then discusses receptors which were apparently activated by bath-applied ligands.  These would have been neuromodulators rather than neurotransmitters.
    102 Related citations
See PubMed abstract page.   

1996    164<349
Rostrocaudal distribution of 5-HT innervation in the lamprey spinal cord and differential effects of 5-HT on fictive locomotion. 
    Neurotransmitter:    5 -HT   
    fictive locomotion = CPG 

1996  161<349
Activation of pharmacologically distinct metabotropic glutamate receptors depresses reticulospinal-evoked monosynaptic EPSPs in the lamprey spinal cord.   
These results provide evidence for the colocalization of at least two different subtypes of presynaptic mGluRs on a single reticulospinal axon in the lamprey. These presynaptic mGluRs could serve as glutamatergic autoreceptors limiting the extent of reticulospinal-mediated excitation of spinal neurons."  
presynaptic mGluR   

Organization of the lamprey striatum - transmitters and projections.    
    The purpose of the present study is to characterize the striatum of the lamprey by immunohistochemical and tracing techniques. Cells immunoreactive for GABA and substance P (SP), and positive for acetylcholinesterase, are present in the lamprey striatum. Immunoreactive (ir) fibers were detected by antisera raised against SP, dopamine, enkephalin and serotonin.  
    These immunoreactive fibers were mainly located in the periventricular neuropil that borders the striatum and in which GABAergic striatal neurons distributed their dendritic arbors.
    Putative connections between the striatum, the ventral part of the lateral pallium, and the diencephalic motor centers involved in the control of locomotion were studied by using fluorescein-coupled dextran amines (FDA) as a tracer. The striatum projects to the ventral part of the lateral pallium (lpv), where GABA-ir cells and SP-ir fibers were also present.  
    The lpv in turn projects to the ventral thalamus, which has descending connections to the reticulospinal cells involved in the control of locomotion.  
    These results, together with previous findings of histaminergic and neurotensin projections, suggest that the lamprey striatum and its inputs with regard to neurotransmitters/modulators are very similar to those of modem amniotes, including primates, and are thus conserved to a high degree."    
    8 Cited by's      

1998    147<349     Free Article   
Substance P modulates NMDA responses and causes long-term protein synthesis-dependent modulation of the lamprey locomotor network.
Substance P 

1998 142<349
Cellular and synaptic modulation underlying substance P-mediated plasticity of the lamprey locomotor network     
Free Article   
   See:  Central Pattern Generators   for full Abstract and link to Free full text. 


Endogenous and exogenous dopamine presynaptically inhibits glutamatergic reticulospinal transmission via an action of D2-receptors on N-type Ca2+ channels.  
In this study, the effects of exogenously applied and endogenously released dopamine (DA), a powerful modulator of the lamprey locomotor network, are examined on excitatory glutamatergic synaptic transmission between reticulospinal axons and spinal neurons.  
    Bath application of DA (1-50 micro m) reduced the amplitude of monosynaptic reticulospinal-evoked glutamatergic excitatory postsynaptic potentials (EPSPs). The effect of DA was blocked by the D2-receptor antagonist eticlopride, and mimicked by the selective D2-receptor agonist 2,10,11 trihydroxy-N-propyl-noraporphine hydrobromide (TNPA). Bath application of the DA reuptake blocker bupropion, which increases the extracellular level of dopamine, also reduced the monosynaptic EPSP amplitude. This effect was also blocked by the D2-receptor antagonist eticlopride.  
    To investigate if the action of DA was exerted at the presynaptic level, the reticulospinal axon action potentials were prolonged by administering K+ channel antagonists while blocking l-type Ca2+ channels. A remaining Ca2+ component, mainly dependent on N and P/Q channels, was depressed by DA. When DA (25-50 micro m) was applied in the presence of omega-conotoxin GVIA, a toxin specific for N-type Ca2+ channels, it failed to affect the monosynaptic EPSP amplitude. DA did not affect the response to extracellularly ejected d-glutamate, the postsynaptic membrane potential, or the electrical component of the EPSPs.  
    DA thus acts at the presynaptic level to modulate reticulospinal transmission."     
    385 Related citations:   
See the paper.   

2003   96<349 
Endogenous dopaminergic modulation of the lamprey spinal locomotor network.

2004    86<349     Free Article  
The spinal GABAergic system is a strong modulator of burst frequency in the lamprey locomotor network          
The spinal network coordinating locomotion is comprised of a core of glutamate and glycine interneurons. This network is modulated by several transmitter systems including spinal GABA interneurons."  
Thus the spinal GABA system does play a prominent role in burst frequency regulation in that it reduces the burst frequency by < or =50%, presumably due to presynaptic and soma-dendritic effects documented previously."  
glutamate, glycine, GABA  
lamprey locomotor network 

Free Article    
5-HT Modulation of identified segmental premotor interneurons in the lamprey spinal cord.

Muscarinic receptor activation elicits sustained, recurring depolarizations in reticulospinal neurons.      
Free PMC Article  
    See:  Lamprey GABA

Development and organization of the descending serotonergic brainstem-spinal projections in the sea lamprey.  
     "The organization and development of the descending spinal projections from serotonergic rhombencephalic neurons in the larval sea lamprey were investigated by double labeling, tract-tracing methods and immunocytochemistry against serotonin. The results showed that two serotonergic populations of the isthmic and vagal reticular regions present reticulospinal neurons from the beginning of the larval period.  
    Of the three serotonergic subpopulations recognized in the isthmic reticular group, only two - the medial and ventral subpopulations - project to the spinal cord, with most of the projecting cells in the caudal part of the medial isthmic subpopulation. Occasional cells projecting to the spinal cord were observed in the ventral subpopulation.  
    The vagal reticular serotonergic nucleus situated in the caudal rhombencephalon also presents cells with descending projections.  
    The early development of the brainstem serotonergic projections to the spinal cord appears to be a conserved trait in all vertebrates studied. Although a serotonergic hindbrain-spinal projection system appears to have been present before the divergence of agnathans and gnathostomes, no serotonergic cells were observed in the raphe region in lamprey. Moreover, proportionally more rostral hindbrain serotonergic cells contribute to the spinal serotonergic projections in the sea lamprey than in jawed vertebrates."
My comment:   
no serotonergic cells were observed in the raphe region in lamprey"      
    So the actions of serotonin in the lamprey are very different from the actions in humans described in   Boys without Fathers  .   
    522 Related citations:   
See the PubMed abstract page.  

Forebrain dopamine depletion impairs motor behavior in lamprey.

The structure of the basal ganglia appears to be conserved throughout vertebrate evolution, with characteristic cellular and transmitter components in each area, and the same types of afferent input. As described in rodents and primates, depletion of the striatal dopamine results in characteristic motor deficits. To explore if this role of the basal ganglia in modulating motor function was present early in vertebrate evolution, we investigated here the effects of striatal dopamine depletion in the lamprey, a cyclostome, which diverged from the main vertebrate line around 560 million years ago. The lamprey striatum contains the same cellular elements as found in mammals, and receives the same types of input, including a prominent dopamine innervation. We show here that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 100 mg/kg i.p.), a neurotoxin, depletes forebrain and striatal dopamine levels in lamprey to 15% of control values, and has profound effects on motor performance. Twenty-four and 48 h after MPTP injection, lampreys demonstrated marked reductions in spontaneous swimming and the duration of each swimming episode. Impairments in the ability to initiate movements were shown by a decreased rate of initiation. Furthermore, the initiation and maintenance of locomotion induced by olfactory mucosa stimulation was severely impaired, as was the coordination of different motor tasks. These deficits were ameliorated by the dopamine agonist apomorphine. The motor deficits arising after striatal dopamine depletion are thus qualitatively similar in cyclostomes and mammals. The role of the dopamine innervation of the striatum thus appears to be conserved throughout vertebrate evolution."  
    10 Cited by's:    

    Serotonin and GABA are colocalized in restricted groups of neurons in the larval sea lamprey brain: insights into the early evolution of neurotransmitter colocalization in vertebrates  
    "Colocalization of the classic neurotransmitters serotonin (5-HT) and gamma-aminobutyric acid (GABA) (or the enzyme that synthesizes the latter, glutamate decarboxylase) has been reported in a few neurons of the rat raphe magnus-obscurus nuclei. However, there are no data on the presence of neurochemically similar neurons in the brain of non-mammalian vertebrates.  
    Lampreys are the oldest extant vertebrates and may provide important data on the phylogeny of neurochemical systems. The colocalization of 5-HT and GABA in neurons of the sea lamprey brain was studied using antibodies directed against 5-HT and GABA and confocal microscopy. Colocalization of the neurotransmitters was observed in the diencephalon and the isthmus.  
    In the diencephalon, about 87% of the serotonergic cells of the rostral tier of the dorsal thalamus (close to the zona limitans) exhibited GABA immunoreactivity. In addition, occasional cells double-labelled for GABA and 5-HT were observed in the hypothalamic tuberal nucleus and the pretectum.  
    Of the three serotonergic isthmic subgroups already recognized in the sea lamprey isthmus (dorsal, medial and ventral), such double-labelled cells were only observed in the ventral subgroup (about 61% of the serotonergic cells in the ventral subgroup exhibited GABA immunoreactivity). An equivalence between these lamprey isthmic cells and the serotonergic/GABAergic raphe cells of mammals is suggested.  
    Present findings suggest that serotonergic/GABAergic neurons are more extensive in lampreys than in the rat and probably appeared before the separation of agnathans and gnathostomes. Cotransmission by release of 5-HT and GABA by the here-described lamprey brain neurons is proposed.
    107 Related citations:   
    Free PMC Article  with many active links.   
    I also got the PDF from the library.     

A parallel cholinergic brainstem pathway for enhancing locomotor drive
    "The brainstem locomotor system is believed to be organized serially from the mesencephalic locomotor region (MLR) to reticulospinal neurons, which in turn project to locomotor neurons in the spinal cord. We identified brainstem muscarinoceptive neurons in lampreys (Petromyzon marinus) that received parallel inputs from the MLR and projected back to reticulospinal cells to amplify and extend the duration of locomotor output. These cells responded to muscarine with extended periods of excitation, received direct muscarinic excitation from the MLR and projected glutamatergic excitation to reticulospinal neurons. Targeted blockade of muscarine receptors over these neurons profoundly reduced MLR-induced excitation of reticulospinal neurons and markedly slowed MLR-evoked locomotion. The presence of these neurons forces us to rethink the organization of supraspinal locomotor control, to include a sustained feedforward loop that boosts locomotor output."
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The dopamine D2 receptor gene in lamprey, its expression in the striatum and cellular effects of D2 receptor activation.   

    "All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role.  
    We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound.  
    We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates."  
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Dopamine differentially modulates the excitability of striatal neurons of the direct and indirect pathways in lamprey.      Free full text 
The functions of the basal ganglia are critically dependent on dopamine. In mammals, dopamine differentially modulates the excitability of the direct and indirect striatal projection neurons, and these populations selectively express dopamine D1 and D2 receptors, respectively. Although the detailed organization of the basal ganglia is conserved throughout the vertebrate phylum, it was unknown whether the differential dopamine modulation of the direct and indirect pathways is present in non-mammalian species. We aim here to determine whether the receptor expression and opposing dopaminergic modulation of the direct and indirect pathways is present in one of the phylogenetically oldest vertebrates, the river lamprey. Using in situ hybridization and patch-clamp recordings, we show that D1 receptors are almost exclusively expressed in the striatal neurons projecting directly to the homolog of the substantia nigra pars reticulata. In addition, the majority of striatal neurons projecting to the homolog of the globus pallidus interna/globus pallidus externa express D1 or D2 receptors. As in mammals, application of dopamine receptor agonists differentially modulates the excitability of these neurons, increasing the excitability of the D1-expressing neurons and decreasing the excitability of D2-expressing neurons. Our results suggest that the segregated expression of the D1 and D2 receptors in the direct and indirect striatal projection neurons has been conserved across the vertebrate phylum. Because dopamine receptor agonists differentially modulate these pathways, increasing the excitability of the direct pathway and decreasing the excitability of the indirect pathway, this organization may be conserved as a mechanism that biases the networks toward action selection."  
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Forebrain dopamine neurons project down to a brainstem region controlling locomotion.
     "The contribution of dopamine (DA) to locomotor control is traditionally attributed to ascending dopaminergic projections from the substantia nigra pars compacta and the ventral tegmental area to the basal ganglia, which in turn project down to the mesencephalic locomotor region (MLR), a brainstem region controlling locomotion in vertebrates. However, a dopaminergic innervation of the pedunculopontine nucleus, considered part of the MLR, was recently identified in the monkey. The origin and role of this dopaminergic input are unknown. We addressed these questions in a basal vertebrate, the lamprey. Here we report a functional descending dopaminergic pathway from the posterior tuberculum (PT; homologous to the substantia nigra pars compacta and/or ventral tegmental area of mammals) to the MLR. By using triple labeling, we found that dopaminergic cells from the PT not only project an ascending pathway to the striatum, but send a descending projection to the MLR. In an isolated brain preparation, PT stimulation elicited excitatory synaptic inputs into patch-clamped MLR cells, accompanied by activity in reticulospinal cells. By using voltammetry coupled with electrophysiological recordings, we demonstrate that PT stimulation evoked DA release in the MLR, together with the activation of reticulospinal cells. In a semi-intact preparation, stimulation of the PT elicited reticulospinal activity together with locomotor movements. Microinjections of a D1 antagonist in the MLR decreased the locomotor output elicited by PT stimulation, whereas injection of DA had an opposite effect. It appears that this descending dopaminergic pathway has a modulatory role on MLR cells that are known to receive glutamatergic projections and promotes locomotor output."
    "It appears that this descending dopaminergic pathway has a modulatory role on MLR cells that are known to receive glutamatergic projections and promotes locomotor output."
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2013    29<349      Free Article   
Dopamine differentially modulates the excitability of striatal neurons of the direct and indirect pathways in lamprey.

Evolutionarily conserved organization of the dopaminergic system in lamprey: SNc/VTA afferent and efferent connectivity and D2 receptor expression.
    "The dopaminergic system influences motor behavior, signals reward and novelty, and is an essential component of the basal ganglia in all vertebrates including the lamprey, one of the phylogenetically oldest vertebrates. The intrinsic organization and function of the lamprey basal ganglia is highly conserved. For instance, the direct and indirect pathways are modulated through dopamine D1 and D2 receptors in lamprey and in mammals. The nucleus of the tuberculum posterior, a homologue of the substantia nigra pars compacta (SNc)/ventral tegmental area (VTA) is present in lamprey, but only scarce data exist about its connectivity. Likewise, the D2 receptor is expressed in the striatum, but little is known about its localization in other brain areas. We used in situ hybridization and tracer injections, both in combination with tyrosine hydroxylase immunohistochemistry, to characterize the SNc/VTA efferent and afferent connectivity, and to relate its projection pattern with D2 receptor expression in particular. We show that most features of the dopaminergic system are highly conserved. As in mammals, the direct pallial (cortex in mammals) input and the basal ganglia connectivity with the SNc/VTA are present as part of the evaluation system, as well as input from the tectum as the evolutionary basis for salience/novelty detection. Moreover, the SNc/VTA receives sensory information from the olfactory bulbs, optic tectum, octavolateral area, and dorsal column nucleus, and it innervates, apart from the nigrostriatal pathway, several motor-related areas. This suggests that the dopaminergic system also contributes to the control of different motor centers at the brainstem level."
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2014   18<986 
Dopamine: a parallel pathway for the modulation of spinal locomotor networks.  
    "The spinal cord contains networks of neurons that can produce locomotor patterns. To readily respond to environmental conditions, these networks must be flexible yet at the same time robust. Neuromodulators play a key role in contributing to network flexibility in a variety of invertebrate and vertebrate networks. For example, neuromodulators contribute to altering intrinsic properties and synaptic weights that, in extreme cases, can lead to neurons switching between networks. Here we focus on the role of dopamine in the control of stepping networks in the spinal cord. We first review the role of dopamine in modulating rhythmic activity in the stomatogastric ganglion (STG) and the leech, since work from these preparations provides a foundation to understand its role in vertebrate systems. We then move to a discussion of dopamine's role in modulation of swimming in aquatic species such as the larval xenopus, lamprey and zebrafish. The control of terrestrial walking in vertebrates by dopamine is less studied and we review current evidence in mammals with a focus on rodent species. We discuss data suggesting that the source of dopamine within the spinal cord is mainly from the A11 area of the diencephalon, and then turn to a discussion of dopamine's role in modulating walking patterns from both in vivo and in vitro preparations. Similar to the descending serotonergic system, the dopaminergic system may serve as a potential target to promote recovery of locomotor function following spinal cord injury (SCI); evidence suggests that dopaminergic agonists can promote recovery of function following SCI. We discuss pharmacogenetic and optogenetic approaches that could be deployed in SCI and their potential tractability. Throughout the review we draw parallels with both noradrenergic and serotonergic modulatory effects on spinal cord networks. In all likelihood, a complementary monoaminergic enhancement strategy should be deployed following SCI.   

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2014   112>667
Serotonergic modulation of post-synaptic inhibition and locomotor alternating pattern in the spinal cord.     
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    See:  Central Pattern Generators  

CotA Lamprey Neurotransmitters
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