Ca2+ requirements for cerebellar long-term synaptic depression:: Role for a postsynaptic leaky integrator

Photolysis of a caged Ca2+ compound was used to characterize the dependence of cerebellar long-term synaptic depression (LTD) on postsynaptic Ca2+ concentration ([Ca2+](i)). Elevating [Ca2+](i) was sufficient to induce LTD without requiring any of the other signals produced by synaptic activity. A sigmoidal relationship between [Ca2+](i) and LTD indicated a highly cooperative triggering of LTD by Ca2+. The duration of the rise in [Ca2+](i) influenced the apparent Ca2+ affinity of LTD, and this time-dependent behavior could be described by a leaky integrator process with a time constant of 0.6 s. A computational model, based on a positive-feedback cycle that includes protein kinase C and MAP kinase, was capable of simulating these properties of Ca2+-triggered LTD. Disrupting this cycle experimentally also produced the predicted changes in the Ca2+ dependence of LTD. We conclude that LTD arises from a mechanism that integrates postsynaptic Ca2+ signals and that this integration may be produced by the positive-feed back cycle.