The number and organization of Ca2+ channels in the active zone shapes neurotransmitter release from schaffer collateral synapses

摘要

Fast synaptic transmission requires tight colocalization of Ca2+channels and neurotransmitter vesicles. It is generally thought that Ca2+ channels are expressed abundantly in presynaptic active zones, that vesicles within the same active zone have similar release properties, and that significant vesicle depletion only occurs at synapses with high release probability. Here we show, at excitatory CA3→CA1 synapses in mouse hippocampus, that release from individual vesicles is generally triggered by only one Ca2+ channel and that only few functional Ca2+ channels may be spread in the active zone at variable distances to neighboring neurotransmitter vesicles. Using morphologically realistic Monte Carlo simulations, we show that this arrangement leads to a widely heterogeneous distribution of release probability across the vesicles docked at the active zone, and that depletion of the vesicles closest to Ca2+ channels can account for the Ca2+ dependence of short-term plasticity at these synapses. These findings challenge the prevailing view that efficient synaptic transmission requires numerous presynaptic Ca2+ channels in the active zone, and indicate that the relative arrangement of Ca2+ channels and vesicles contributes to the heterogeneity of release probability within and across synapses and to vesicle depletion at small central synapses with low average release probability.