Modeling a Neural Circuit for Flexible Control of Innate Behaviors

The adaptive control of social behaviors, such as aggression and reproduction, is a critical function of the nervous system. In the past decade, new methods for genetically targeted functional manipulation and imaging of neural activity have proven phenomenally fruitful in identifying neural subpopulations that play a role in expression of social behaviors. But our understanding of how these neural populations work together in a behaving animal remains highly fractured. In the proposed work, we develop a computational approach to integrate neural imaging data from multiple genetically targeted neural populations and construct a circuit model of social behavior control. A significant challenge in studying social behavior is its high variability and complexity, features that defy traditional trial-averaging-based analyses of neural activity. To address this challenge, we will leverage our recently developed automated tracking system to build a quantitative and detailed model of social behaviors and sensory processing in pairs of freely interacting mice. This behavior model will provide the basis for a thorough statistical analysis of neural dynamics within and between a collection of four subcortical nuclei, which together span three putative layers of processing, the first just past the sensory periphery and the last just upstream of premotor populations in the periaqueductal gray. This analysis will include 1) predicting animals’ future behavior from joint neural and behavioral models, 2) characterizing behavior tuning of individual neurons in each nucleus with a linear-nonlinear model, and 3) fitting a network model to imaging data from multiple nuclei, and testing predicted connectivity from this model with a novel optogenetic perturbation system. Finally, we will build on these analyses to address the flexibility of behavior control by network models of subcortical nuclei. In the K99 phase, this research plan will allow me to develop advanced skills in the use