Research in the Littleton lab is aimed at characterizing the mechanisms by which neurons form synaptic connections, how synapses transmit information, and how synapses change during learning and memory. Our lab combines molecular biology, protein biochemistry, electrophysiology, and neuroimaging approaches with Drosophila genetics to address these questions. A major effort has been to characterize the molecular machinery that mediates synaptic vesicle fusion, focusing on how the calcium sensor Synaptotagmin and the fusion clamp Complexin interface with the SNARE complex to control neurotransmitter release. Our lab has also developed transgenic tools to spatially visualize synaptic vesicle fusion events at single active zones (AZs), defining general rules for how individual release sites function and identifing a new category of “spontaneous only” AZs that revealed novel roles for minis in synaptic development and function.