Sunday, May 18, 2025
5/18/2025
Cellular and circuit basis for flexible control of sensory acquisition - Project Summary The goal of this project is to study the cellular and circuit bases of motor control for active sensation. Accurate and context-specific movements of sensors is critical for acquiring sensory information during behavior. This requires coordination of ongoing sensory information and motor output, often across different levels of processing in the brain. However, these circuits can be complicated and difficult to access at the molecular and cellular level. Studying their function in either normal or disease states is thereby a major challenge. Fruit flies (Drosophila melanogaster) actively tune mechanosensory input using movements of their two antennae, and our recent work has expanded genetic access to the sensory and motor circuits in this small circuit model system. With a broad suite of genetic, physiological, and neural connectivity tools to study neural circuits in Drosophila, our project seeks to reveal mechanisms of motor control for sensation at the cellular and circuit levels. First, we will establish the role of a newly discovered set of antennal premotor neurons in controlling specific antennal movements during behavior. We will use a combination of optogenetics and in vivo electrophysiology in tethered, flying flies to determine how cellular activity in these neurons coordinates movement. Using supervised machine learning tools to analyze antennal video data recorded simultaneously with neural recordings, we will quantify the activity of individual genetically identified neurons in response to external deflections of the antennae and to self-generated motions during flight. Next, we will directly measure how actively controlled antennal movements alter sensitivity of an antennal mechanosensory neuron class, using a combination of in vivo electrophysiology and mechanical manipulations of active antennal movements. Finally, we will identify and characterize new descending neurons that project to antennal motor neurons in the central brain before synapsing onto motor output regions controlling wing and leg movements. We will use stochastic optogenetic activation with quantitative behavior analysis to map their role in producing distinct antennal motions, then evaluate the functional connectivity of these neurons with antennal motor neurons using optogenetic activation and intracellular recordings in intact, behaving animals. Together, this work will elucidate cellular strategies for coordinated tuning of sensation during behavior.
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