Over the past eight years, my lab has pioneered studies of the acoustic communication system of Drosophila, to address fundamental questions related to the neural mechanisms underlying sensory perception and the generation of behaviors. Similar to other animals, flies produce and process patterned sounds during their mating ritual. Using a combination of novel behavioral assays, neural circuit perturbations, neural recordings, and computational modeling, we discovered that male song structure and intensity are continually sculpted by interactions with the female, over timescales ranging from tens of milliseconds to minutes. Building on this finding, we have gone on to dissect the neural mechanisms underlying the visual modulation of song patterning in males. Using a similar set of tools, we have also interrogated the female side of acoustic communication, and have successfully related song representations along the auditory pathway to changes in locomotor behavior, again across multiple timescales. My lab has developed several new methods to facilitate these studies, including methods for tracking and segmenting animal behavior, for population neural imaging, and for single-cell transcriptomics in the Drosophila brain. Our system and discoveries lay the essential foundation for now solving the bigger challenge of how an animal's internal state and experiences contribute to shaping these neural mechanisms. To do so, we will employ new computational models to identify the neural correlates of internal state. We will also use a new paradigm to induce learning during acoustic communication, and will characterize how learning shapes sensorimotor integration in this system. Finally, we will manipulate the hunger or arousal status of flies to determine, again at the cellular level, how long timescale modulation of neural activity shapes fast timescale sensorimotor processes. These new research directions will leverage the methods we have optimized for the recording and analysis of neural and behavioral data, in addition to incorporating new methods for recording activity in behaving flies that experience naturalistic, multimodal courtship stimuli timed to their movements on a spherical treadmill. What we discover in this system will reveal fundamental principles regarding how brains mediate perceptions, thoughts, actions, and ultimately the ability to communicate with another individual.

Public Health Relevance

This proposal leverages the Drosophila model system to address the neural mechanisms underlying social interactions, from processing of cues emitted by a communication partner to generating complex behaviors in response to those cues. Impairments in processing sensory information or generating motor behaviors, particularly in the context of social interactions, underlie several human disorders including Parkinson's disease and Autism spectrum disorder. This proposal will uncover general principles of neural circuit function that will inform studies of sensorimotor integration in more complex systems.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Unknown (R35)
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Special Emphasis Panel (ZNS1)
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David, Karen Kate
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Princeton University
Schools of Arts and Sciences
United States
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