Frequency‐dependent N‐methyl‐D‐aspartate receptor‐mediated synaptic transmission in rat hippocampus.

Abstract

1. The effects of the N‐methyl‐D‐aspartate (NMDA) antagonist, D‐2‐amino‐5‐phosphonovalerate (APV) were examined on synaptic responses evoked by high‐frequency stimulation of the Schaffer collateral‐commissural pathway, in the presence of Mg2+ (1 or 2 mM) and functional synaptic inhibition. 2. The synaptic response evoked by 100 Hz stimulation comprised fast excitatory postsynaptic potentials (EPSPs) evoked by each shock and a slow depolarization. APV reduced the size of the depolarization without depressing the fast EPSPs. 3. The mean (+/‐ 1 S.E.) amplitude of the APV‐sensitive component (3.0 +/‐ 0.3 mV), evoked by 100 Hz stimulation at membrane potentials near rest, was invariably smaller than the first fast EPSP (9.8 +/‐ 0.7 mV). Both of these synaptic components had similar thresholds and increased in amplitude as the stimulus intensity was raised. There was a positive correlation between the amplitude of the two components (r = 0.57, P less than 0.01). 4. The amplitude of the APV‐sensitive component was positively correlated (r = 0.97, P less than 0.05) with the frequency of stimulation during the trains (between 10 and 100 Hz). The threshold frequency for evoking an APV‐sensitive component was approximately 10 Hz. 5. In contrast to the fast EPSPs the amplitude of the APV‐sensitive component increased with depolarization, and decreased with hyperpolarization, of a neurone from its resting membrane potential. The component was no longer present in some cells which had been hyperpolarized sufficiently. 6. It is suggested that during high‐frequency stimulation a neurone may become depolarized for a sufficient time to reduce the Mg2+ block of NMDA channels. This enables the NMDA receptor system to contribute transiently to the synaptic response, despite the inhibitory synaptic mechanisms which prevent its activation during single‐shock stimulation. The characteristics of the NMDA receptor‐mediated synaptic response may explain properties relating to the induction of long‐term potentiation (LTP).