GLYCINE REGULATION OF SYNAPTIC NMDA RECEPTORS IN HIPPOCAMPAL-NEURONS

1. Although glycine has been identified as a required coagonist with g lutamate at N-methyl-D-aspartate (NMDA) receptors, the understanding o f glycine's role in excitatory synaptic: neurotransmission is quite li mited. In the present study, we used the whole cell patch-clamp techni que to examine the ability of glycine to regulate current flow through synaptic NMDA receptors at excitatory synapses between cultured hippo campal neurons and in acutely isolated hippocampal slices. 2. These st udies demonstrate that the glycine modulatory site on the synaptic NMD A receptor is not saturated under baseline conditions and that increas ed glycine concentrations can markedly increase NMDA-receptor-mediated excitatory postsynaptic currents (EPSCs) in hippocampal neurons in bo th dissociated cell culture and in slice. Saturation of the maximal ef fect of glycine takes place at different concentrations for different cells in culture, suggesting the presence of heterogenous NMDA recepto r subunit compositions. 3. Bath-applied glycine had no effect on the t ime course of EPSCs in either brain slice or culture, indicating that desensitization of the NMDA receptor is not prevented by glycine over the time course of an EPSC. 4. When extracellular glycine concentratio n is high, all miniature EPSCs recorded in the cultured hippocampal ne urons contained NMDA components, indicating that segregation of non NM DA receptors at individual synaptic boutons does not occur.