Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF-GluR2 interaction

We investigated whether the interaction between the N-ethyl-maleimide-sensi tive fusion protein (NSF) and the AMPA receptor (AMPAR) subunit GluR2 is in volved in synaptic plasticity in the CA1 region of the hippocampus. Blockad e of the NSF-GluR2 interaction by a specific peptide (pep2m) introduced int o neurons prevented homosynaptic, de novo long-term depression (LTD). Moreo ver, saturation of LTD prevented the pep2m-induced reduction in AMPAR-media ted excitatory postsynaptic currents (EPSCs). Minimal stimulation experimen ts indicated that both pep2m action and LTD were due to changes in quantal size and quantal content but were not associated with changes in AMPAR sing le-channel conductance or EPSC kinetics. These results suggest that there i s a pool of AMPARs dependent on the NSF-GluR2 interaction and that LTD expr ession involves the removal of these receptors from synapses.