Rodent 5-HT3R

Cross reference:  Serotonin Gate (5-HT3R)       Rodent 5-HT1R 
Rodent Hormone-Nerve Interaction     Serotonin References        

FINAL SUMMARY
OF 5 REFERENCES
1993 - 2005


    "Between 70 and 95% of the 5-HT3R-expressing cells were GABAergic throughout the telencephalon." 
    "
Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.



INITIAL SUMMARIES
OF THE REFERENCES



Following are initial summaries of the references.  The references are designated by the first words of their title and their year of publication.   

The references themselves follow this list of their initial summaries. 


Nervous system distribution ... 1993 
    "This distribution suggests that 5-HT3 receptors may mediate the known serotonergic inhibition of pyramidal cell populations via excitation of inhibitory interneurons."   
 


The 5-HT3 receptor is present in different ... 1997  
    "Between 70 and 95% of the 5-HT3R-expressing cells were GABAergic throughout the telencephalon."    


The central 5-HT3 receptor in CNS disorders ... 1998    
   
"... 5-HT3R-expressing neurons are mainly GABA containing cells in the rat neocortex, olfactory cortex, hippocampus, and amygdala which also often contain cholecystokinin (CCK) immunoreactivity.


In Vivo Excitation of GABA Interneurons ... 2004  
    "Here we report that the physiological stimulation of the raphe nuclei excites local, putatively GABAergic neurons in the prelimbic and cingulate areas of the rat PFC in vivo."  
    "
Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.



Molecular diversity of neocortical GABAergic ... 2005  
    "In addition to being the main source of inhibition in the adult brain, GABAergic interneurones are instrumental in pacing the activity of large ensembles of principal cells. GABAergic interneurones have unique features that enable them to contribute to the generation of synchronized network activity thereby shaping principal cell behaviour."


THE REFERENCES


Nervous system distribution of the serotonin 5-HT3 receptor mRNA
(Goog) - 1993    
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC45887/pdf/pnas01102-0301.pdf
Full length PDF available online for free. 
    "Antagonists of this receptor have anxiolytic and antiemetic effects in humans and in animal models.
   
To determine with cellular resolution the distribution of 5-HT3 receptor mRNA, in situ hybridization was performed in sections of mouse brain and
dorsal root ganglia. Scattered labeled cells were observed throughout cortical regions, with highest densities in the piriform, cingulate, and entorhinal areas. Strong hybridization signals were seen in the hippocampal formation, where expression appeared primarily in interneurons. Labeled cells were most abundant in the posteroventral hippocampal region, particularly in the lacunosum moleculare layer of CAL.
    This distribution suggests that 5-HT3 receptors may mediate the known serotonergic inhibition of pyramidal cell populations via excitation of inhibitory interneurons.
    Labeled cells were also observed in the major subdivisions of the amygdaloid complex, the olfactory bulb, the trochlear nerve nucleus, the dorsal tegmental region, the facial nerve nucleus, the nucleus of the spinal tract of the trigeminal nerve, and the spinal cord dorsal horn. In the periphery, intense hybridization signals were seen in a subpopulation of cells in dorsal root ganglia.

My comment
    It's going to be very difficult to work backwards in evolution from this wide distribution of 5-HT3R in the mouse brain to the amphioxus.  


The 5-HT3 receptor is present in different subpopulations of GABAergic neurons in the rat telencephalon  (PubMed) - 1997    
http://www.ncbi.nlm.nih.gov/pubmed/9096150       
    Reference from "In vivo ... 2004".   
Full-length PDF and HTML available online for free.
  
from the abstract       
   
"The type 3 serotonin receptor (5-HT3R) is a ligand-gated ion channel whose presence in the CNS has been established by radioligand binding, in situ hybridization, and immunohistochemical analysis."   
    "We used in situ hybridization and immunocytochemistry to determine that 5-HT3R-expressing neurons are mainly GABA-containing cells in the rat telencephalon. 
We determined that 5-HT3R/GABA-containing neurons do not exhibit somatostatin immunoreactivity but often contain cholecystokinin (CCK) immunoreactivity."   
    "
We suggest that serotonin through the 5-HT3R may regulate GABA and CCK neurotransmission in the telencephalon."    
   
"Between 70 and 95% of the 5-HT3R-expressing cells were GABAergic throughout the telencephalon."    
   
"In conclusion, we demonstrated that the 5-HT3R-expressing neurons are mainly GABAergic in the rat telencephalon, suggesting that depolarization of these cells by serotonin might regulate inhibitory and disinhibitory circuits in the rat telencephalon.
   
The HTML was followed by a long list of other, related, articles. 


The central 5-HT3 receptor in CNS disorders (PubMed) - 1998    
http://www.ncbi.nlm.nih.gov/pubmed/9566603 
Only abstract available online. 
"...
5-HT3R-expressing neurons are mainly GABA containing cells in the rat neocortex, olfactory cortex, hippocampus, and amygdala which also often contain cholecystokinin (CCK) immunoreactivity.



In Vivo Excitation of GABA Interneurons in the Medial Prefrontal Cortex through 5-HT3 Receptors - 2004  
http://cercor.oxfordjournals.org/cgi/content/full/14/12/1365 
Full length HTML and PDF available online for free. 
    This HTML included many active links to other articles. 
from the abstract       
   
"Here we report that the physiological stimulation of the raphe nuclei excites local, putatively GABAergic neurons in the prelimbic and cingulate areas of the rat PFC in vivo."  
    "These excitations had a latency of 36 ± 4 ms and a duration of 69 ± 9 ms and were blocked by the i.v. administration of the 5-HT3 receptor antagonists ondansetron and tropisetron."  
My 1st comment
    5-HT3R is ionotropic.  I was under the impression that the ligand, in this case 5-HT, of an ionotropic receptor acts as a neurotransmitter rather than as a neuromodulator and that it must be delivered to the receptor across the synaptic cleft.  If 5-HT3R responds to a 5-HTR antagonist which is administrated intravenously, then perhaps I was mistaken.  Perhaps, all the results of agonists or antagonists of ionotropic receptors involve neuromodulation.   Do ionotropic receptors always respond to ligand which is circulating in the blood stream? 
more from the abstract        
    "The latency and duration were shorter than those elicited through 5-HT2A receptors in pyramidal neurons of the same areas. Double in situ hybridization histochemistry showed the presence of GABAergic neurons expressing 5-HT3 receptor mRNA in PFC."   
My 2nd comment
    The shorter latency supports the view that the receptors are ionotropic and, therefore, 5-HT3R.  The paper doesn't provide the time lag between the intravenous injections of the 5-HT3R antagonists and the blocking of the short latency excitations of the GABAergic neurons, nor does it give any idea of the dose of the injection.  Perhaps if there's enough ligand circulating in the blood for long enough, some of it eventually leaks over to the synaptic cleft, thereby modulating the response of ionotropic neurotransmitter receptors.   

more from the abstract     
   
"Double in situ hybridization histochemistry showed the presence of GABAergic neurons expressing 5-HT3 receptor mRNA in pre-frontal cortex (PFC).
    "
Overall, these results support an important role of 5-HT in the control of the excitability of apical dendrites of pyramidal neurons in the medial PFC through the activation of 5-HT3 receptors in GABAergic interneurons.

My 3rd comment
    The introduction is a review of many different articles, and does not specify the species on which the earlier data was obtained.  The newly reported experimental data was obtained on ratsThe presence of 5-HT1A and 5-HT2A receptors along with the newly identified 5-HT3 receptors on the pyramidal cell dendrites in the rat prefrontal cortex greatly complicates the analysis. 



Molecular diversity of neocortical GABAergic interneurones - 2005    
    Abstract       
    HTML
http://jp.physoc.org/content/562/1/99.full   
    Reference from "
The 5-HT3 receptor is present ... 1997"   
F
ull-length PDF and HTML available online for free.   
from the abstract       
    "
In addition to being the main source of inhibition in the adult brain, GABAergic interneurones are instrumental in pacing the activity of large ensembles of principal cells. GABAergic interneurones have unique features that enable them to contribute to the generation of synchronized network activity thereby shaping principal cell behaviour.
"
    "
5-HT3R, the only ionotropic serotonin receptor, is expressed in a subset of GABAergic interneurones, namely the cholecystokinin (CCK)/VIP-positive neurones.
" 
    "a number of modulatory effects mediated by nicotinic, 5-HT3 or CB1 receptors are exerted both in the neocortex as well as in the hippocampus exclusively or preponderantly on the GABAergic system." 

    This is a review of many different articles.  Although it does not specify the species on which the experimental data was obtained, it is clear that every one had a cortex.  








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