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The Journal of Neuroscience, April 1, 2000, 20(7):2451-2458

Synaptic Activity Modulates the Induction of Bidirectional Synaptic Changes in Adult Mouse Hippocampus

Anaclet Ngezahayo¹, Melitta Schachner^{1, 2}, and Alain Artola¹

¹ Department of Neurobiology, Swiss Federal Institute of Technology Zürich, Hönggerberg, CH-8093 Zürich, Switzerland, and ² Zentrum für Molekulare Neurobiologie, Universität Hamburg, D-20246 Hamburg, Germany

Activity-dependent synaptic plasticity is critical for learning and memory. Considerable attention has been paid to mechanisms that increase or decrease synaptic efficacy, referred to as long-term potentiation (LTP) and long-term depression (LTD), respectively. It is becoming apparent that synaptic activity also modulates the ability to elicit subsequent synaptic changes. We provide direct experimental evidence that this modulation is attributable, at least in part, to variations in the level of postsynaptic depolarization required for inducing plasticity. In slices from adult hippocampal CA1, a brief pairing protocol known to produce LTP can also induce LTD. The voltage-response function for the induction of LTD and LTP in naive synapses exhibits three parts: at a postsynaptic membrane potential during pairing (V_m)  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, LTP is generated. This function varies with initial synaptic efficacy. In depressed synapses, , the V_m above which LTD is generated, is shifted toward more depolarized V_ms and ⁺, the LTD-LTP crossover point or, equivalently, the V_m above which LTP is induced, toward more polarized V_ms. Conversely in potentiated synapses, is shifted toward more polarized V_ms. Therefore synaptic activity changes synaptic efficacy and accordingly adjusts the voltages for eliciting subsequent synaptic modifications. The concomitant shifts in the voltages for inducing LTD and LTP in opposite directions promote synaptic potentiation and inhibit synaptic depression in depressed synapses and vice versa in potentiated synapses.

Key words: long-term potentiation; long-term depression; activity-dependent modulation of LTD-LTP induction; hippocampus; CA1; mouse

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Copyright © 2000 Society for Neuroscience  0270-6474/00/2072451-08$05.00/0

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