A stochastic model of active zone material mediated synaptic vesicle docking and priming at resting active zones

Synaptic vesicles (SVs) fuse with the presynaptic membrane (PM) at specialized regions called active zones for synaptic transmission. SVs are associated with dense aggregates of macromolecules called active zone material (AZM) that has been thought to be involved in SV release. However, its role has recently begun to be elucidated. Several morphological studies proposed distinctively different AZM mediated SV docking and priming models: sequential and concurrent SV docking/priming. To explore ways to reconcile the contradictory models we develop a stochastic AZM mediated SV docking and priming model. We assume that the position of each connection site of the AZM macromolecules on their SV, directly linking the SV with the PM, varies by random shortening and lengthening of the macromolecules at resting active zones. We also perform computer simulations of SVs near the PM at resting active zones, and the results show that the distribution of the AZM connection sites can significantly affect the SV’s docking efficiency and distribution of its contact area with the PM, thus priming and that the area correlates with the shape of the SVs providing a way to account for seemingly irreconcilable observations reported about the spatial relationship of SVs with the PM at active zones.