Vesicular release probability sets the strength of individual Schaffer collateral synapses

Information processing in the brain is controlled by quantal release of neurotransmitters, a tightly regulated process. From ultrastructural analysis, it is known that presynaptic boutons along single axons differ in the number of vesicles docked at the active zone. It is not clear whether the probability of these vesicles to get released ( p ves ) is homogenous or also varies between individual boutons. Here, we optically measure evoked transmitter release at individual Schaffer collateral synapses at different calcium concentrations, using the genetically encoded glutamate sensor iGluSnFR. Fitting a binomial model to measured response amplitude distributions allowed us to extract the quantal parameters N, p ves , a n d q . We find that Schaffer collateral boutons typically release single vesicles under low p ves conditions and switch to multivesicular release in high calcium saline. Analyzing the variability of quantal parameters, we conclude that the vesicular release probability rather than the number of readily releasable vesicles or their transmitter content determines the potency of individual boutons.