Surface expression of AMPA receptors in hippocampal neurons is regulated by an NSF-dependent mechanism

Here, we show that disruption of N-ethylmaleimide-sensitive fusion protein- (NSF-) GluR2 interaction by infusion into cultured hippocampal neurons of a blocking peptide (pep2m) caused a rapid decrease in the frequency but no c hange in the amplitude of AMPA receptor-mediated miniature excitatory posts ynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mE PSCs were not changed. Viral expression of pep2m reduced the surface expres sion of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors , whereas NMDA receptor surface expression in the same living cells was unc hanged. In permeabilized neurons, the total amount of GluR2 immunoreactivit y was unchanged, and a punctate distribution of GluR2 was observed througho ut the dendritic tree. These data suggest that the NSF-GluR2 interaction is required for the surface expression of GluR2-containing AMPA receptors and that disruption of the interaction leads to the functional elimination of AMPA receptors at synapses.