A Monte Carlo simulation dissecting quantal release at the calyx of Held.

Although quantal release provides a basic control of synaptic strength, its underlying mechanisms remain unclear. Here, we report a refined realistic 3D vesicle fusion model at calyx-type synapses. By refining the micro ultrastructure and combining updated parameters, our model is appropriate for simulating quantal release. First, we confirmed the existence of kiss-and-run fusion and gave a justified estimation of its percentage in spontaneous and stimulated release. Second, we found the location of AMPA receptors caused the huge variation in the mEPSC rise time. Third, glutamate spillover only slightly contributed to the mEPSC decay time in small vesicles but caused a dual-peak event in large vesicles. Fourth, mEPSC rise time increased with amplitude, suggesting the contribution of vesicle size, not glutamate concentration. We also applied our model to the analysis of KCl, CaCl2 and synaptotagmin-2 triggered exocytosis. KCl globally accelerated the mEPSCs, whereas mEPSCs were slowed down in high calcium treatments and synaptotagmin-2 knock-out mice, indicating more kiss-and-run release. In summary, our model provides a convenient method for exploring the detailed mechanism of vesicle fusion.