Abstract
Central mammalian synapses release synaptic vesicles in dedicated structures called docking/release sites. It has been assumed that when voltage-dependent calcium entry is sufficiently large, synaptic output attains a maximum value of one synaptic vesicle per action potential and per site. Here we use deconvolution to count synaptic vesicle output at single sites (mean site number per synapse: 3.6). When increasing calcium entry with tetraethylammonium in 1.5 mM external calcium concentration, we find that synaptic output saturates at 0.22 vesicle per site, not at 1 vesicle per site. Fitting the results with current models of calcium-dependent exocytosis indicates that the 0.22 vesicle limit reflects the probability of docking sites to be occupied by synaptic vesicles at rest, as only docked vesicles can be released. With 3 mM external calcium, the maximum output per site increases to 0.47, indicating an increase in docking site occupancy as a function of external calcium concentration.
Highlights
The release of synaptic vesicles (SVs) at mammalian central synapses is a complex process that comprises two series of events
SVs move to a small part of the presynaptic terminal, the active zone (AZ), where they bind to specific proteins such as RIM and Munc13, and undergo a number of maturation steps including docking and priming (Sudhof, 2012; Jahn and Fasshauer, 2012)
In this work we examine counts of SV release events measured in simple parallel fibers (PFs)-molecular layer interneurons (MLIs) synapses when increasing the release probability with several methods
Summary
The release of synaptic vesicles (SVs) at mammalian central synapses is a complex process that comprises two series of events. The sensitivity of the exocytosis step to Cai results from the change of conformation of the SNARE complex following rapid Ca2+ binding to a series of Ca2+ binding sites residing on synaptotagmins (Jahn and Fasshauer, 2012). At high Cai values, the response saturates, presumably because all available SVs undergo exocytosis. Based on these findings, various multistep kinetic models of SV release have been proposed, where the probability of exocytosis reaches a maximum of 1 for high Cai values (Bollmann et al, 2000; Schneggenburger and Neher, 2000; Lou et al, 2005)
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