D-2-amino-5-phosphonovaleate blocks induction of long-term depression of the NMDA receptor-mediated synaptic component in rat hippocampus

Abstract

The long-term depression (LTD) of pharmacologically isolated N- methyl- d-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSP NMDA) was studied in an 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 μM) and picrotoxin (50 μM) 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 μM) suggesting that the induction of LTD requires an increase in postsynaptic Ca 2+, at least in part, due to synaptic activation of NMDA receptors during concomitant postsynaptic depolarization.