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-feedback cycle.