ACTIVITY REGULATES THE SYNAPTIC LOCALIZATION OF THE NMDA RECEPTOR IN HIPPOCAMPAL-NEURONS

We describe here a novel effect of activity on the subcellular distrib ution of NMDA receptors in hippocampal neurons in culture. In spontane ously active neurons, NMDA receptors were clustered at a few synaptic and nonsynaptic sites. Chronic blockade of NMDA receptor activity indu ced a 380% increase in the number of NMDA receptor clusters and a shif t to a more synaptic distribution. This effect was reversible. The dis tributions of the presynaptic marker synaptophysin, the AMPA-type glut amate receptor subunit GluR1, and the putative NMDA receptor clusterin g protein PSD-95 were not affected by blockade. Regulation of the syna ptic localization of NMDA receptors by activity may define a novel mec hanism by which input controls a neuron's ability to modify its synaps es.