Bistable Switches for Synaptic Plasticity

Nearly a decade intervened between theoretical prediction and experimental verification of the mechanisms underlying synaptic plasticity. A persistent decrease in synaptic efficacy, called long-term depression (LTD), of the parallel fiber–Purkinje cell synapse is thought to underlie some forms of learning and memory in the cerebellum. Simulation studies predicted that mitogen-activated protein kinase and protein kinase C would mutually activate each other and make a bistable positive feedback loop, thereby providing a molecular basis for LTD. This claim stimulated experimenters to successfully demonstrate the feedback loop and its pivotal role in cerebellar LTD.

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