A frequency-dependent mobilization of heterogeneous pools of synaptic vesicles shapes presynaptic plasticity

The segregation of the readily releasable pool of synaptic vesicles (RRP) in sub-pool which are differentially poised for exocytosis shapes short-term plasticity at depressing synapses. Here, we used in vitro recording and modeling of synaptic activity at the facilitating mice cerebellar granule cell to Purkinje cell synapse to demonstrate the existence of two sub-pools of vesicles in the RRP that can be differentially recruited upon fast changes in the stimulation frequency. We show that upon low-frequency stimulation, a population of fully-releasable vesicles is silenced, leading to full blockage of synaptic transmission. A second population of vesicles, reluctant to release by simple stimuli, is recruited in a millisecond time scale by high-frequency stimulation to support an ultrafast recovery of neurotransmitter release after low-frequency depression. The frequency-dependent mobilization or silencing of sub-pools of vesicles in granule cell terminals should play a major role in the filtering of sensorimotor information in the cerebellum.