Independent Regulation of Basal Neurotransmitter Release Efficacy by Variable Ca2+ Influx and Bouton Size at Small Central Synapses

The efficacy of action potential evoked neurotransmitter release varies widely even among synapses supplied by the same axon,and the number of release-ready vesicles at each synapse is a major determinant of this heterogeneity. here we identify a second,equally important,mechanism for release heterogeneity at small hippocampal synapses,the inter-synaptic variation of the exocytosis probability of release-ready vesicles. using concurrent measurements of vesicular pool sizes,vesicular exocytosis rates,and presynaptic ca2+ dynamics,in the same small hippocampal boutons,we show that the average fusion probability of release-ready vesicles varies among synapses supplied by the same axon with the size of the spike-evoked ca2+ concentration transient. we further show that synapses with a high vesicular release probability exhibit a lower ca2+ cooperativity,arguing that this is a direct consequence of increased ca2+ influx at the active zone. we conclude that variability of neurotransmitter release under basal conditions at small central synapses is accounted for not only by the number of release-ready vesicles,but also by their fusion probabilities,which are set independently of bouton size by variable spike-evoked presynaptic ca2+ influx. © 2012 ermolyuk et al.