Inertia of Synaptic Vesicle Exocytosis

Abstract

Reliable synaptic vesicle exocytosis in primary hippocampal neurons depends on the number and availability of release-competent vesicles, their recharging with neurotransmitters and the kinetics of exo- endocytosis. We have analyzed the correlations between several exocytotic kinetic parameters by measuring FM-styryl dyes (FM 1-43, FM 4-64 and FM 5-95) discharge from electrically stimulated synapses: initial fluorescence, relative fluorescence loss, half-decay time and number of neighbors of each synapse. All terminals were maximally loaded and subsequently destained by three different stimulations, using 1200 action potentials (APs) at frequency of 40 Hz for loading and 600 APs at 30 Hz, 20 Hz and 10 Hz for destaining, respectively. Nerve terminals that contain more dye and thus more vesicles released styryl dyes slower compared to synapses that contain fewer vesicles. Furthermore, vesicle-rich synapses exhibited a lesser relative fluorescence loss than those with fewer vesicles. Interestingly, synapses with more neighbors matched these with high initial fluorescence . Computer model simulations revealed that the results of the exocytosis parameter measurements were not compromised by statistical and system-specific appraisal artifacts. The results of this study show that exocytosis is qualitatively and quantitatively different in vesicle-rich and vesicle-poor synapses and depends on the spatial localisation of the synapse and their number of neighbors, respectively. This variation could be the basis for specific information-processing circuits in the hippocampus.