Proteomic and Functional Analysis of Presynaptic Physiology and Plasticity

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ABSTRACT The molecular mechanisms of plasticity within the presynapse and its role in behaviors such as learning and memory are still poorly understood, mainly due to a lack of knowledge of the signaling molecules of the presynaptic cytomatrix and tools to spatially and temporally manipulate presynaptic plasticity. This gap in knowledge is a fundamental barrier to the field. In this project, we will develop and utilize innovative proteomic, genome editing, and optogenetic approaches to solve these problems, revealing the proteins and inner workings of the cytomatrix of presynapses from distinct neuronal cell types and their roles in learning and memory. We anticipate these data will provide a new and unparalleled molecular framework for future studies on presynaptic physiology as well as insights into how forms of presynaptic plasticity modulate behavior.