Physiology and plasticity of the active zone in vivo

突触是专门的细胞间接触部位，作为神经元和它们的伙伴细胞之间的通信联系。在化学突触中，钙离子（Ca 2+）的流入触发了载有递质的囊泡与突触前膜在称为活动区的特定亚细胞区域的融合。由该过程释放的递质物质然后扩散穿过突触间隙，并被突触后受体感知以传递信号转导。突触传递的一个标志是它的可塑性，它使突触能够通过过滤、修改或整合信息来调节复杂的大脑过程。然而，活动区生理学的细节及其调节如何有助于突触可塑性，却几乎不为人所知。通过将遗传学与高分辨率的光和电生理学方法相结合，在果蝇，该项目将测试的假设，即活动区的生理活动诱导的可塑性在体内修改。为此，分子动力学将遵循单突触分辨率，神经传递将在一个完整的，活着的，遗传上最顺从的生物体中被诱发和测量。

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.