Although vesicle depletion contributes to short-term depression, several studies have reported that the release probability can be transiently depressed even if an action potential fails to evoke release. Here we argue that stochastic fluctuation in the release machinery can give rise to apparent release-independent depression as a result of sampling bias. The relationship between this apparent depression and the interstimulus interval provides a window on the kinetics of state transitions of the release apparatus.
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