Pair recordings reveal all-silent synaptic connections and the postsynaptic expression of long-term potentiation

The activation of silent synapses is a proposed mechanism to account for ra pid increases in synaptic efficacy such as long-term potentiation (LTP). Us ing simultaneous recordings from individual pre- and postsynaptic neurons i n organotypic hippocampal slices, we show that two CA3 neurons can be conne cted entirely by silent synapses. Increasing release probability or applica tion of cyclothiazide does not produce responses from these silent synapses . Direct measurement of NMDAR-mediated postsynaptic responses in all-silent synaptic connections before and after LTP induction show no change in fail ure rate, amplitude. or area. These data do not support hypotheses that syn apse silent results from presynaptic factors or that LTP results from incre ases in presynaptic glutamate release. LTP is also associated with an incre ase in postsynaptic responsiveness to exogenous AMPA. We conclude that syna pse silence, activation, and expression of LTP are postsynaptic.