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Activity-induced synaptic modification is essential for the development and plasticity of the nervous system^,,. Repetitive correlated activation of pre- and postsynaptic neurons can induce persistent enhancement or decrement of synaptic efficacy, commonly referred to as long-term potentiation or depression^,(LTP or LTD). An important unresolved issue is whether and to what extent LTP and LTD are restricted to the activated synapses^,,,,. Here we show that, in the CA1 region of the hippocampus, reduction of postsynaptic calcium influx by partial blockade of NMDA (N-methyl-d-aspartate) receptors results in a conversion of LTP to LTD and a loss of input specificity normally associated with LTP, with LTD appearing at heterosynaptic inputs. The induction of LTD at homo- and heterosynaptic sites requires functional ryanodine receptors and inositol triphosphate (InsP₃) receptors, respectively. Functional blockade or …