Identification of a novel process limiting the rate of synaptic vesicle cycling at hippocampal synapses

During intense presynaptic activity, the readily releasable pool (RRP) of s ynaptic vesicles empties more quickly than it can be refilled, and short-te rm depression results. Ordinarily, the pool refills within 20 s, but long, high-frequency trains of action potentials often induce a form of shout-ter m depression that persists for a much longer time. Here, we report that rep lenishment of the RRP is governed by two simple processes: the previously i dentified mechanism termed refilling, and another process that appears afte r extensive exocytosis and produces a transient decrease in the capacity of the pool, lasting for several minutes. The data presented here place strin gent constraints on the types of kinetic models that can be used to describ e synaptic vesicular cycling and are inconsistent with the traditional mult ipool models of vesicular mobilization.