D-2-AMINO-5-PHOSPHONOVALEATE BLOCKS INDUCTION OF LONG-TERM DEPRESSIONOF THE NMDA RECEPTOR-MEDIATED SYNAPTIC COMPONENT IN RAT HIPPOCAMPUS

The long-term depression (LTD) of pharmacologically isolated N-methyl- D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSP(NMDA)) was studied in an in vitro slice preparation of rat hipp ocampus. Intracellular recordings were made from CA1 pyramidal cells i n the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 muM) and picrotoxin (50 muM) which block non-NMDA and GABA(A) receptors, re spectively. Low frequency (1 Hz) synaptic stimulation caused a transie nt decrease in the amplitude of EPSP(NMDA) that usually restored to it s control level within 15 min after the stimulation. However, pairing of low frequency synaptic stimulation with postsynaptic depolarization induced an LTD of EPSP(NMDA). The EPSP(NMDA) LTD could be blocked by D-2-amino-5-phosphonovaleate (D-APV, 20 muM) suggesting that the induc tion of LTD requires an increase in postsynaptic Ca2+, at least in par t, due to synaptic activation of NMDA receptors during concomitant pos tsynaptic depolarization.