Synaptic activity modulates the induction of bidirectional synaptic changes in adult mouse hippocampus

Activity-dependent synaptic plasticity is critical for learning and memory. Considerable attention has been paid to mechanisms that increase or decrea se synaptic efficacy, referred to as longterm potentiation (LTP) and long-t erm depression (LTD), respectively. It is becoming apparent that synaptic a ctivity also modulates the ability to elicit subsequent synaptic changes. W e provide direct experimental evidence that this modulation is attributable , at least in part, to variations in the level of postsynaptic depolarizati on required for inducing plasticity. In slices from adult hippocampal CA1, a brief pairing protocol known to produce LTP can also induce LTD. The volt age-response function for the induction of LTD and LTP in naive synapses ex hibits three parts: at a postsynaptic membrane potential during pairing (V- m) less than or equal to -40 mV, no synaptic modification is obtained; at V -m between -40 and -20 mV, LTD is induced; and, finally, at V-m > -20 mV, L TP is generated. This function varies with initial synaptic efficacy. In de pressed synapses, Theta(-), the V-m above which LTD is generated, is shifte d toward more depolarized Vms and Theta(+), the LTD-LTP crossover point or, equivalently, the V-m above which LTP is induced, toward more polarized Vm s. Conversely in potentiated synapses, Theta(-) is shifted toward more pola rized V-ms. Therefore synaptic activity changes synaptic efficacy and accor dingly adjusts the voltages for eliciting subsequent synaptic modifications . The concomitant shifts in the voltages for inducing LTD and LTP in opposi te directions promote synaptic potentiation and inhibit synaptic depression in depressed synapses and vice versa in potentiated synapses.