Two Ca2+-dependent steps controlling synaptic vesicle fusion and replenishment at the cerebellar basket cell terminal

Cerebellar basket cells inhibit postsynaptic Purkinje cells in a rapid and precise manner. To investigate the mechanisms of transmitter release underlying this rapid inhibition, Ca2+ uncaging was employed to measure the intracellular Ca2+ dependence of transmitter release and the kinetics of synaptic vesicle pool transitions in immature basket cell synapses at room temperature. Vesicle release properties distinct from those previously observed at excitatory synapses were seen, including a relatively high intracellular Ca2+ sensitivity of vesicle fusion, rapid vesicle pool mobilization with few reluctant vesicles, and vesicle replenishment driven by unusually high Ca2+ levels from both local and residual Ca2+ sources during action potential trains. These results suggest that inhibitory basket cell synapses are optimized for rapid and precise temporal and spatial Ca2+ coordination of synaptic vesicle fusion and replenishment, which may contribute to the unique physiology of inhibitory synaptic transmission, including phasic release during action potential trains and tonic release by residual intracellular Ca2+.