Calcium‐dependent inactivation of the monosynaptic NMDA EPSCs in rat hippocampal neurons in culture

The effects of increased dendritic calcium concentration ([Ca2+]i) induced by single action potentials on monosynaptic glutamatergic excitatory postsynaptic currents (EPSCs) were studied in cultured rat hippocampal neurons. To investigate the respective roles of pre‐ and postsynaptic elements in the depolarization‐induced NMDAR inactivation, we have performed simultaneous paired whole‐cell recordings from monosynaptically connected pre‐ and postsynaptic hippocampal neurons. We report that the single firing of the postsynaptic neuron did not result in inactivation of the NMDAR‐EPSC, whereas a burst of depolarizing steps transiently depressed the NMDAR‐EPSCs in both pyramidal cells and interneurons. This effect was mediated by postsynaptic voltage‐gated Ca2+ influx, as it was prevented by: (i) buffering postsynaptic [Ca2+]i with 30 m m BAPTA; (ii) removing extracellular Ca2+; or (iii) applying Cd2+o (100 μm), a voltage‐gated calcium channel blocker. It does not involve presynaptic mechanisms as it selectively affected NMDA but not α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA) receptor‐mediated EPSCs. These results suggest that inactivation of NMDAR‐channels by voltage‐gated Ca influx is a general property of hippocampal neurons, which may play an important role in reducing postsynaptic NMDAR Ca2+ influx that leads to plasticity or excitotoxicity during sustained neuronal activity.

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