Long-term potentiation (LTP) has received attention because of its proposed role in learning and memory. Despite substantial effort the pre- or postsynaptic expression site of LTP remains unsettled. It has been proposed that LTP is expressed postsynaptically through the functional conversion of “silent synapses.” We had shown that Schaffer collateral (SC) silent and “functional synapses,” which lack and express AMPA receptors, respectively exhibit distinct transmitter release properties. Therefore the functional conversion of silent synapses with LTP should be associated with presynaptic modifications. We now show that the pairing-induced LTP at SC synapses is mediated by combined pre- and postsynaptic modifications involving the postsynaptic emergence of an AMPA response coupled with an enhanced glutamate release. BDNF replicates the changes associated with this LTP by activating TrkBRs, suggesting that the neurotrophin is required for the coordinated changes on both sides of the synaptic cleft. © 2010 Wiley-Liss, Inc.