Glycine Regulation of Synaptic NMDA Receptors in Hippocampal Neurons.
Wilcox, K. S., R. Maki Fitzsimonds, B. Johnson, M. A. Dichter.
Depts of Neurology and Pharmacology, and David Mahoney Institute for
Neurological Sciences, University of Pennsylvania, Philadelphia, PA 19104.
APStracts 3:0154N, 1996.
SUMMARY AND CONCLUSIONS
1. Although glycine has been identified as a required coagonist with glutamate
at NMDA receptors, the understanding of glycine's role in excitatory synaptic
neurotransmission is quite limited. In the present study, we used the whole
cell patch clamp technique to examine the ability of glycine to regulate
current flow through synaptic NMDA receptors at excitatory synapses between
cultured hippocampal neurons and in acutely isolated hippocampal slices. 2.
These studies demonstrate that the glycine modulatory site on the synaptic
NMDA receptor is not saturated under baseline conditions and that increased
glycine concentrations can markedly increase NMDA-receptor mediated excitatory
postsynaptic currents (EPSCs) in hippocampal neurons in both dissociated cell
culture and in slice. Saturation of the maximal effect of glycine takes place
at different concentrations for different cells in culture, suggesting the
presence of heterogenous NMDA receptor subunit compositions. 3. Bath applied
glycine had no effect on the time course of EPSCs in either brain slice or
culture, indicating that desensitization of the NMDA receptor is not prevented
by glycine over the timecourse of an EPSC. 4. When extracellular glycine
concentration is high, all miniature EPSCs recorded in the cultured
hippocampal neurons contained NMDA components, indicating that segregation of
non-NMDA receptors at individual synaptic boutons does not occur.
Received 29 January 1996; accepted in final form 24 June 1996.
APS Manuscript Number J65-6.
Article publication pending J. Neurophysiol.
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996