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.
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