Summary

Recent work has suggested that some proportion of excitatory synapses on hippocampal CA1 pyramidal cells that express NMOA receptors (NMDARa) may not express functional AMPA receptors (AMPARs), thus making these synapses silent at the resting membrane potential. In agreement with this hypothesis, we dem-onstrete here that it is pQssible to stimulate synapses that yield no detectable excitatory postsynaptic cur-rents (EPSCs) when the cell is held at- 60 mV; yet at positive holding potentials (+30 to +60 mV), EPSCs can be elicited that are completely blocked by the NMOAR antagonist, D-APV. When these functionally silent syn-apses are subjected to an LTP Induction protocol, EPSCs mediated by AMPARs appear and remain for the duration of the experiment. This conversion of silent synapses to functional synapses is blocked by D-APV. These results suggest that LTP may involve modifica-tion of AMPARs that, prior to LTP, were either not pres-ent in the postsynaptic membrane or electrophysiolog-ically silent. This mechanism may account for several experimental results previously attributed to presyn-aptic changes in quantal content