Document Detail


In vivo modulation of N-methyl-D-aspartate receptor-dependent long-term potentiation by the glycine modulatory site.
MedLine Citation:
PMID:  1347648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The role of the glycine modulatory site in N-methyl-D-aspartate receptor function was examined by determining the effect of the glycine site antagonist, 7-chlorokynurenic acid, on the induction of long-term potentiation at the commissural-CA1 synapse in anesthetized rats. Robust long-term potentiation of population excitatory postsynaptic potentials and population spike responses recorded extracellularly in the stratum pyramidale and in stratum radiatum of CA1 developed after high frequency stimulation (100 Hz for 1 s) of commissural fibers during continuous intrahippocampal administration of vehicle solution (0.15 M NaCl). In contrast, infusion of either 7-chlorokynurenic acid (400 microM) or of the N-methyl-D-aspartate receptor antagonist, D-2-amino-5-phosphonovaleric acid (100 microM), significantly attenuated or completely blocked the development of long-term potentiation. When 7-chlorokynurenic acid was infused together with the glycine analog, D-serine (1 mM), long-term potentiation developed that was comparable to that observed in control animals. Intrahippocampal administration of D-serine alone was associated with slightly greater magnitude of long-term potentiation than observed in control animals. Collectively, these findings establish that in intact hippocampus, activity at the glycine modulatory site is necessary for activation of the N-methyl-D-aspartate receptor complex. Furthermore, these results suggest that the glycine modulatory site may not be fully saturated in vivo, and thus can serve to regulate N-methyl-D-aspartate receptor function.
Authors:
E Thiels; D J Weisz; T W Berger
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Neuroscience     Volume:  46     ISSN:  0306-4522     ISO Abbreviation:  Neuroscience     Publication Date:  1992  
Date Detail:
Created Date:  1992-04-13     Completed Date:  1992-04-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  501-9     Citation Subset:  IM    
Affiliation:
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
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MeSH Terms
Descriptor/Qualifier:
2-Amino-5-phosphonovalerate / pharmacology
Anesthesia
Animals
Electric Stimulation
Evoked Potentials / physiology
Hippocampus / drug effects,  physiology*
Kynurenic Acid / analogs & derivatives,  pharmacology
Male
Rats
Rats, Inbred Strains
Receptors, Glycine
Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors,  drug effects,  physiology*
Receptors, Neurotransmitter / drug effects,  physiology*
Serine / pharmacology
Synapses / physiology
Grant Support
ID/Acronym/Agency:
MH-00343/MH/NIMH NIH HHS; MH-45156/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Receptors, Glycine; 0/Receptors, N-Methyl-D-Aspartate; 0/Receptors, Neurotransmitter; 18000-24-3/7-chlorokynurenic acid; 492-27-3/Kynurenic Acid; 56-45-1/Serine; 76726-92-6/2-Amino-5-phosphonovalerate

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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