CAREER: Neural Control of Proceptivity in Drosophila

Social behavior requires individuals to both respond to others and take the initiative to interact. Knowing when to act and when to react is essential for finding mates, avoiding conflict, cooperating, and navigating everyday social life. Yet how the brain selects the appropriate mode of behavior in different situations remains one of the central questions in neuroscience. This project addresses that question using the fruit fly, Drosophila melanogaster, a powerful model organism with a rich behavioral repertoire, a completely mapped brain, and exceptional tools that allow researchers to study neural circuits with unprecedented precision. The project builds on a newly developed approach that uses light to control social interactions in real time. By optogenetically restricting the movements of a courting male while allowing the female to move freely, the researchers can separate proactive social behaviors initiated by the female from reactive behaviors driven by the male. This approach makes it possible to identify how sensory information, internal state, and specific brain circuits interact to guide social behavior. Advanced optical imaging will reveal how neurons process these signals in behaving animals, providing new insight into how brains generate flexible social behavior. Because balancing proactive and reactive interactions is a universal challenge shared across animal species, including humans, the principles uncovered in this work are expected to extend far beyond flies and advance our understanding of the neural basis of social behavior. A hands-on neuroscience module introducing optogenetics will be developed for high school students, and a Course-based Undergraduate Research Experience (CURE) will provide students with authentic research experiences in neural circuit mapping, optogenetics, and artificial intelligence-based behavioral analysis. In addition, a public podcast exploring the science of social behavior across biological systems, from fruit flies to humans to artificial intelligence, will make discoveries accessible to broad audiences. Together these activities will expand access to research training, strengthen scientific literacy, and help prepare the next generation of scientists while advancing fundamental knowledge about how brains make social decisions. This project advances NSF’s priorities in Biotechnology and Artificial Intelligence. Sexual selection theory identifies female mate choice as a central evolutionary force, but its neural basis is poorly understood. Mechanistic work in Drosophila has focused on male courtship and female receptivity, not proactive female behavior. The project overcomes this limitation with an opto-tethering paradigm: a male is optogenetically confined to half of the arena by closed-loop tracking, decoupling proactive (female-initiated) from reactive (male-driven) behavior at high resolution. Aim 1 tests how sensory input, mating status, and social context shape proceptivity through sensory and internal-state manipulations. Aim 2 tests how higher-order neurons integrate internal state and sensory cues during proactive versus reactive courtship, combining cell-type-specific perturbations with two-photon calcium imaging in behaving animals. Together the aims establish a framework for disentangling reactive vs proactive social behavior in a genetically tractable system with a fully mapped brain, revealing how internal state and sensory information converge to drive social decisions. 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.