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.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project--Cooperative Agreements (U01)
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Special Emphasis Panel (ZNS1-SRB-S (61))
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Gnadt, James W
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California Institute of Technology
Schools of Arts and Sciences
United States
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Chen, Chin-Lin; Hermans, Laura; Viswanathan, Meera C et al. (2018) Imaging neural activity in the ventral nerve cord of behaving adult Drosophila. Nat Commun 9:4390
Patella, Paola; Wilson, Rachel I (2018) Functional Maps of Mechanosensory Features in the Drosophila Brain. Curr Biol 28:1189-1203.e5
van Breugel, Floris; Huda, Ainul; Dickinson, Michael H (2018) Distinct activity-gated pathways mediate attraction and aversion to CO2 in Drosophila. Nature 564:420-424
Azevedo, Anthony W; Wilson, Rachel I (2017) Active Mechanisms of Vibration Encoding and Frequency Filtering in Central Mechanosensory Neurons. Neuron 96:446-460.e9
Schnell, Bettina; Ros, Ivo G; Dickinson, Michael H (2017) A Descending Neuron Correlated with the Rapid Steering Maneuvers of Flying Drosophila. Curr Biol 27:1200-1205
Bell, Joseph S; Wilson, Rachel I (2016) Behavior Reveals Selective Summation and Max Pooling among Olfactory Processing Channels. Neuron 91:425-38
Suver, Marie P; Huda, Ainul; Iwasaki, Nicole et al. (2016) An Array of Descending Visual Interneurons Encoding Self-Motion in Drosophila. J Neurosci 36:11768-11780
Tuthill, John C; Wilson, Rachel I (2016) Parallel Transformation of Tactile Signals in Central Circuits of Drosophila. Cell 164:1046-59
Weir, Peter T; Henze, Miriam J; Bleul, Christiane et al. (2016) Anatomical Reconstruction and Functional Imaging Reveal an Ordered Array of Skylight Polarization Detectors in Drosophila. J Neurosci 36:5397-404
Mendes, César S; Bartos, Imre; Márka, Zsuzsanna et al. (2015) Quantification of gait parameters in freely walking rodents. BMC Biol 13:50

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