DESCRIPTION (provided by applicant): The goal of the project team is to develop a robust, multi-lab research framework, enabled by large scale imaging, which will lead to principled integrative models of ethologically-relevant behaviors that incorporate a detailed knowledge of individual cell classes. The specific neurobiological question that the team will address is how the brain integrates sensory information in order to guide locomotion in a particular direction. Our strategy is to systematically map and functionally characterize the neural circuits that underlie goal-directed locomotion, using the fruit fly, Drosophila, in order to exploit the convergence of powerful genetic, optical, behavioral, and analytical tools that are available in this species. The proposal focuses primarily on refining functional imaging approaches to map the activity of small brain regions and populations of individual neurons in intact, behaving animals while they respond to a controlled panel of sensory stimuli. We have constructed a strategic plan consisting of seven interrelated research modules that create a flow for discovery that starts with functional imaging and ends with the development of integrative models for sensory-guided behavior. The goal of this proposal is to bring all research modules to the requisite level of maturity for future research. To achieve this goal this project will develop robust, quantitative and high throughput methods for: Functional 2-photon imaging using pan-neural drivers. ArcLight imaging using selected driver lines. Functional 2-photon imaging using pan-neural drivers. Circuit analysis of sensory motor pathways. And a plan for an integrative computational model of sensory-guided locomotion.

PUBLIC HEALTH RELEVANCE: Understanding sensory-motor integration should lead to a better understanding of the pathophysiology of movement disorders in human patients, including Parkinson's disease, stroke, and spinal cord injury. Furthermore, understanding how the brain processes sensory information and uses it to direct movements can aid in the design and optimization of robotic prosthetic limbs, and in the longer term, may also contribute to the development of prosthetic devices for replacement of damaged sensory modalities.