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

Neuron. 1999 Jun;23(2):365-76. doi: 10.1016/s0896-6273(00)80786-2.


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 change in the amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). N-methyl-D-aspartate (NMDA) receptor-mediated mEPSCs were not changed. Viral expression of pep2m reduced the surface expression of alpha-amino-3-hydroxy-5-methyl-isoxazolepropionate (AMPA) receptors, whereas NMDA receptor surface expression in the same living cells was unchanged. In permeabilized neurons, the total amount of GluR2 immunoreactivity was unchanged, and a punctate distribution of GluR2 was observed throughout 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Carrier Proteins / physiology*
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / physiology
  • Hippocampus / cytology
  • Hippocampus / metabolism*
  • Hippocampus / ultrastructure
  • Immunoblotting
  • Immunohistochemistry
  • N-Ethylmaleimide-Sensitive Proteins
  • Neurons / metabolism*
  • Neurons / ultrastructure
  • Rats
  • Receptors, AMPA / biosynthesis*
  • Receptors, AMPA / metabolism
  • Receptors, AMPA / physiology
  • Receptors, N-Methyl-D-Aspartate / biosynthesis
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Synaptic Membranes / physiology
  • Synaptophysin / metabolism
  • Transfection
  • Vesicular Transport Proteins*


  • Carrier Proteins
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Synaptophysin
  • Vesicular Transport Proteins
  • glutamate receptor ionotropic, AMPA 4
  • N-Ethylmaleimide-Sensitive Proteins
  • Nsf protein, rat
  • glutamate receptor ionotropic, AMPA 2
  • glutamate receptor ionotropic, AMPA 1