Sex hormone regulation of Lateral Habenula circuitry for reward and aversion encoding

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Project Summary This proposal seeks to investigate sex hormone effects on reward and aversion-related behaviors through mapping of Lateral Habenula (LHb) circuits. The LHb is a central hub important for encoding aversive information and coordinating motivated behaviors, actions critical for survival. Dysfunction in LHb-dependent circuits contribute to a diverse set of disordered behaviors, such as aberrant processing of positive and negative valence, anhedonia, depressive symptomology, and maladaptive stress response, to name a few. While it is known that motivated behaviors are modulated by circulating sex hormones, no studies have investigated whether negative circuit regulators, specifically projections from the LHb, contribute to this phenomenon. Furthermore, nuclear hormone receptors in the brain have not been well characterized, therefore understanding their role within LHb reward circuits and how they interact with circulating hormones will provide insight into mechanisms driving sex hormone effects on reward-related behaviors. In this proposal, by taking advantage of the most recent technologies to define, manipulate, and monitor neural activity, I plan to test the functional contribution of specific hormone receptors on molecularly defined LHb projection neurons on reward and aversion-related behaviors.