Using an Optical Sensor of Synaptic Vesicle Exocytosis to Investigate the Relationship Between Release Probability and Paired-Pulse Plasticity at Individual Hippocampal Synapses

Abstract

Release probability (Pr) is a determinant of synaptic strength that varies considerably between synapses, and correlates with the size of the readily releasable pool (RRP) of synaptic vesicles. Short-term plasticity is quantified in electrophysiological experiments by measuring the paired-pulse ratio (PPR) of postsynaptic current amplitudes in response to two successive stimuli. An inverse relationship has been reported between population-averaged values of Pr and PPR, but this relationship has not yet been examined at the level of individual release sites. We utilized a genetically encoded fluorescent sensor to directly measure Pr, PPR, and RRP size at synapses in dissociated cultures of rat hippocampal neurons. We propose that processes affecting vesicular release probability, i.e. the likelihood that individual synaptic vesicles in the RRP undergo exocytosis, inversely alter Pr and PPR. In contrast, mechanisms modulating the number of synaptic vesicles in the RRP may regulate Pr without affecting PPR.