Rapid, activation-induced redistribution of ionotropic glutamate receptorsin cultured hippocampal neurons

We have examined the membrane localization of an AMPA receptor subunit (Glu R1) and an NMDA receptor subunit (NR1) endogenously expressed in primary cu ltures of rat hippocampal neurons. In unstimulated cultures, both GluR1 and NR1 subunits were concentrated in SV2-positive synaptic clusters associate d with dendritic shafts and spines. Within 5 min after the addition of 100 mu M glutamate to the culture medium, a rapid and selective redistribution of GluR1 subunits away from a subset of synaptic sites was observed. This r edistribution of GluR1 subunits was also induced by AMPA, did not require N MDA receptor activation, did not result from ligand-induced neurotoxicity, and was reversible after the removal of agonist. The activation-induced red istribution of GluR1 subunits was associated with a pronounced (similar to 50%) decrease in the frequency of miniature EPSCs, consistent with a role o f GluR1 subunit redistribution in mediating rapid regulation of synaptic ef ficacy. We conclude that ionotropic glutamate receptors are regulated in na tive neurons by rapid, subtype-specific membrane trafficking, which may mod ulate synaptic transmission in response to physiological or pathophysiologi cal activation.