Using evolutionary variation to probe the neural basis for behavior

Animals exhibit astonishing diversity in their behavior, yet almost nothing is known about how evolutionary variation in neural circuits gives rise to species-specific behavioral variation. Here I propose to take advantage of recent advances in genome editing and develop an innovative approach to reveal how evolution sculpts brain circuits. Using CRISPR genome editing technology, we are translating neurogenetic tools from D. melanogaster to other Drosophila species, allowing for the first high-resolution anatomic and functional neural circuit mapping across species. By directly comparing the homologous sensory processing pathways in closely related drosophilids, we will precisely pinpoint where adaptive changes have occurred within the nervous system to produce species-specific mate preferences. The rapid evolution of Drosophila courtship allows us to systematically probe how parallel changes in behavior have been independently implemented in different species, shedding light on the types of changes that are permissible and preferable within brain circuits. Mapping the sites of anatomic and functional change within these pathways will further enable us to study their underlying molecular basis, using transcriptional profiling of the relevant neural populations to provide a definitive link between genetic and behavioral variation. Together, the proposed studies will transform our understanding of the molecular, cellular, and circuit-level changes that generate adaptive behavioral variation across species. As the etiology of many brain disorders is aberrant neural circuit wiring, a deeper understanding of the link between genes, neural circuits, and behavior could have profound consequences for mental health.