Recording and Modeling Brain-wide Neuronal Activity of the Drosophila Pupal Ecdysis Sequence
U.S. National Institute Of Mental Health, Bethesda MD
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Abstract
? DESCRIPTION (provided by applicant): Behavior is the result of patterned activity in motor neurons produced by the action of central neural circuits. Abnormalities in these circuits lead to behavioral disorders in a way that is poorly understood because the circuits themselves are complex and highly distributed. The fruitfly nervous system, like humans', uses ensembles of single neurons to produce complex behaviors, but it is small enough to permit brain-wide circuit analysis at cellular resolution using emerging methods in microscopy. The purpose of this proposal is to comprehensively characterize the neural circuit in a fruitfly that governs a behavioral program, called the ecdysis sequence, using brain-wide imaging with a custom-designed dual-view selective plane illumination microscope (diSPIM). The ecdysis sequence is induced by Ecdysis Triggering Hormone, which acts on approximately 300 neurons that express the Ecdysis Triggering Hormone receptor (ETHR). We hypothesize that patterned activity within these neurons drives motor neuron activity to generate the ecdysis sequence. Using the diSPIM together with recently developed genetic targeting techniques, we will simultaneously measure Ca2+ activity in ETHR-expressing neurons and motor neurons and create spatiotemporal maps of their activity. These maps will, in turn, be used to generate a predictive model of the circuit underlying the ecdysis sequence at cellular resolution. This work should significantly inform our understanding of how neural circuits control coordinated behavior, and thus lead to a better understanding of behavioral disorders.
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