D-2-AMINO-5-PHOSPHONOVALEATE BLOCKS INDUCTION OF LONG-TERM DEPRESSION OF 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 hippocampus. Intracellular recordings were made from CA1 pyramidal cells in 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, respectively. Low frequency (1 Hz) synaptic stimulation caused a transient decrease in the amplitude of EPSP(NMDA) that usually restored to its 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 induction of LTD requires an increase in postsynaptic Ca2+, at least in part, due to synaptic activation of NMDA receptors during concomitant postsynaptic depolarization.