Neurotransmitter release is a specialized form of vesicle fusion that shares a common SNARE-mediated fusion mechanism with other vesicle trafficking pathways within cells. With the appearance of multicellular organisms and just before of the formation of the primitive nervous system, two principal families of SNARE complex-binding proteins emerged, synaptotagmins and complexins. Current data suggest that SNARE binding by the two proteins allows Synaptotagmin 1 to promote fusion in a calcium dependent manner, while complexin prevents premature fusion in the absence of calcium influx. However, their precise roles in regulated secretion and effects on short-term synaptic plasticity are poorly understood. My research is focused on a thorough analysis of synaptic transmission at NMJs of mutant and overexpression animals using high fidelity current recordings of postsynaptic evoked and spontaneous currents using voltage-clamp at the Drosophila NMJ. We are combining quantal analysis with immunocytochemical determination of the number of release sites, allowing a robust description of release properties regulated by complexin and synaptotagmin.