A multisensory-motor integration circuit; from synapse to behavior

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Natural behaviors are a coordinated symphony of motor acts which cause self-induced sensory activation. Sensory neurons only signal presence and magnitude of a sensory cue; they cannot disambiguate self-induced from externally-induced inputs (e.g. hearing your voice versus someone else’s voice). Nevertheless, animals readily differentiate between these sources of sensory signals; this is fundamental to appropriate decision making and adaptive behavioral outcomes. Nervous systems differentiate sources of sensory signals via corollary discharge circuits, which are a broad class of neural circuits that convey a “corollary” of motor commands to sensory neural systems, modifying sensory processing. However, little is known about the cellular and molecular mechanisms that make corollary discharge circuits work. The objective of this project is to characterize the structure and function of a pair of related corollary discharge circuits, comprised of two pairs of identified histaminergic neurons. Establishing a mechanistic framework by which corollary discharges modify sensory function to optimize sensory-motor performance will address long standing gaps in knowledge of how the nervous system integrates sensory-motor information. The research will contribute to the broader study of goal-directed and sensory-guided decision making in animals, robotics, unmanned vehicles, and other engineering applications where movement can interact with sensor function. Additionally, this proposal contains broader societal impacts, STEM training for undergraduate and graduate students in West Virginia, and the development of curriculum for next generation neuroanatomical studies.This project seeks to resolve the cellular and synaptic mechanisms that drive the activity of corollary discharge circuits and the consequences of this activity for sensory-motor performance. To achieve this, experiments will be conducted to: 1) identify upstream and downstream partners of 2 pairs of histaminergic neurons using serial section electron microscopy-based volumetric reconstructions of fly brain and ventral nerve cord coupled with molecular genetic techniques; 2) determine how up- and downstream partners interact with the histamine neurons using optogenetics and Ca2+ imaging during ongoing behavior in highly restricted driver lines, and 3) determine the role of the histamine neurons in shaping sensory-motor performance in behavioral assays. The working hypothesis is that the histamine neurons are primarily activated by descending motor command neurons resulting in downstream suppression of distinct but related sensory networks in the brain. The rationale for this project is that by precisely dissecting interactions between the histamine neurons and their synaptic partners in specific behavioral contexts, a better understand of how corollary discharge circuits integrate and distribute information to fine-tune multisensory-motor interactions during complex natural behaviors. By establishing a mechanistic framework by which corollary discharges modify sensory function to optimize sensory-motor performance, this project provides knowledge of how nervous systems integrate sensory-motor information and contributes to the study of goal-directed and sensory-guided decision making, that can be applied in both biological and engineered applications. This this project will expose students to STEM training and provide new courseware for the emerging field of connectomics.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.