Hippocampal modulation of subcortical circuits in the control of emotional behavior

Project Summary Almost a third of adult Americans suffer from an anxiety disorder, carrying an enormous personal, societal and financial burden. Anxiety disorders are complex circuit-based conditions, resulting from dysfunction in a number of distributed regions, connections, and cell types that generate normal adaptive behavior. Thus, a deeper understanding of how these neural circuits become disrupted to generate maladaptive behavior is crucial if we hope to generate new treatments. In recent years, we have shown that the ventral hippocampus (vHPC) is an central node in the extended circuit that generates adaptive avoidance behavior. However, the input- output organization of the ventral hippocampus in the control of anxiety-related behavior remains poorly understood. Here, we will use functional imaging of large populations of anatomically defined vHPC neurons, optical manipulation of these neurons, and high resolution behavioral analyses to expand our understanding of how the extended ventral hippocampal network controls behavior. We will first determine the encoding properties of vHPC output neurons to subcortical areas known to drive avoidance and anxiety-like behavior. Then, we will adopt new unsupervised behavioral classification tools for understanding anxiety-related behavior in mice to determine how vHPC projection neurons orchestrate distinct behavioral states. Finally, we will determine how distinct inputs to the differentially modulate avoidance behavior and shape anxiety-related representations in vHPC. This will provide the most detailed functional map of the extended hippocampal circuit that controls avoidance behavior, and provide novel targets for generation of therapeutics for the treatment of anxiety disorders.