Physiology and plasticity of the active zone in vivo

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Synapses are specialised intercellular contact sites, which serve as the communication link between neurons and their partner cells. At chemical synapses, calcium-ion (Ca2+) influx triggers the fusion of transmitter-laden vesicles with the presynaptic membrane at a specific sub-cellular region termed the active zone. Transmitter substances released by this process then diffuse across the synaptic cleft and are sensed by postsynaptic receptors to convey signal transduction. A hallmark of synaptic transmission is its plasticity, which enables synapses to regulate complex brain processes by filtering, modifying, or integrating information. The details of active zone physiology and how its modulation contributes to synaptic plasticity are, however, barely understood. By combining genetics with highresolution opto- and electrophysiological methods in Drosophila melanogaster, this project will test the hypothesis that active zone physiology is modified during activity-induced plasticity in vivo. To this end, molecular dynamics will be followed at single synapse resolution and neurotransmission will be both evoked and measured in an intact, alive, and genetically most amenable organism.