POSTSYNAPTIC MODULATION OF NMDA SYNAPTIC CURRENTS IN RAT HIPPOCAMPAL MICROCULTURES BY PAIRED-PULSE STIMULATION

1. Paired-pulse synaptic stimulation of hippocampal neurons in microcu ltures resulted in depression of synaptic currents mediated by both NM DA and alpha amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) rec eptors. However, NMDA EPSCs were more severely depressed than AMPA EPS Cs. 2. Partial NMDA receptor blockade reduced paired-pulse depression of NMDA but not of AMPA synaptic currents while partial AMPA receptor blockade had no effect on paired-pulse depression of AMPA EPSCs. These results suggest that ion flux through NMDA receptors is important in paired-pulse depression of NMDA responses but has no effect on AMPA re sponses. 3. Low extracellular Ca2+ concentrations or positive postsyna ptic holding potentials reduced paired-pulse depression of NMDA EPSCs to near that of AMPA responses. 4. Brief paired applications of exogen ous glutamate to neurons produced Ca2+-dependent depression similar to the depression of NMDA synaptic responses and synaptic stimulation de pressed responses to exogenously applied NMDA. 5. Physiological concen trations of Mg2+ presented expression of the postsynaptic modulation o f NMDA EPSCs at -70 mV, but partial relief of Mg2+ block of the NMDA c hannel with depolarization increased paired-pulse depression of NMDA E PSCs.