ACTIVATION OF NMDA RECEPTORS IN HIPPOCAMPAL AREA CA1 BY LOW AND HIGH-FREQUENCY ORTHODROMIC STIMULATION AND THEIR CONTRIBUTION TO INDUCTION OF LONG-TERM POTENTIATION

N-methyl-D-aspartate (NMDA) receptors are important in many instances of synaptic plasticity. In hippocampal area CA1, long-term potentiatio n (LTP) can be induced by both NMDA receptor-dependent and -independen t mechanisms. Using intracellular recordings and single-electrode volt age clamp, we isolated and characterized NMDA receptor-mediated synapt ic responses. NMDA receptor-mediated responses evoked by low frequency orthodromic stimulation were inhibited in a dose-dependent manner by the competitive antagonist D,L-2-amino-5-phosphonovaleric acid (APV). High frequency (tetanic) stimulation, which facilitates synaptic relea se of glutamate, failed to overcome the blockade of NMDA receptors by APV. Using extracellular recordings of field potentials, we studied th e contribution of NMDA receptors to LTP induced by different patterns of tetanic stimulation. LTP was inhibited in a dose-dependent manner b y APV, but was more sensitive to APV than were NMDA receptor-mediated synaptic responses. This most likely reflects a threshold for NMDA rec eptor activation in LTP induction. A component of LTP that resisted bl ockade by APV was induced by high (200 Hz), but not low (25 Hz), frequ ency tetanization. This NMDA receptor-independent component of LTP per sisted for > 4 hours and accounted for approximately half the potentia tion induced by 200 Hz tetanization. Procedures necessary to induce LT P at the Schaffer collateral/commissural synapses in area CA1 by both NMDA receptor-dependent and -independent mechanisms are now well chara cterized. Using the same neuronal population, it will be possible to a sk if processes involved in the maintenance of LTP are shared even whe n LTP is induced through two different mechanisms. (C) 1994 Wiley-Liss , Inc.