Characterization of Sexual Dimorphism in the Brain

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Project Summary/Abstract The goal of our grant application is a functional and anatomic dissection of the mouse bed nucleus of the stria terminalis (BNST). This nucleus regulates many behaviors, including social approach and interactions, response to predators, coping with physiological and behavioral stressors, and reward responses. The BNST is heterogeneous and contains many neuronal pools with distinct identities. One hypothesis to account for the functional diversity of the BNST is that different BNST neuronal pools serve distinct functions. Our previous work (funded by prior grant periods) and that of others has identified a population of aromatase expressing neurons located in the medial division posteromedial component of the BNST (BNSTmpm). Both aromatase and the BNST are critical for social interactions in males and females. Intriguingly, our work shows that there are more aromatase+ neurons in the BNSTmpm in males compared to females. We therefore hypothesize that aromatase+ BNSTmpm neurons influence the distinct social interactions displayed by the two sexes. In Aim 1, we will use genetically targeted tools to map the connectivity and stimulus responsivity of BNSTmpm neurons in males and females. In Aim 2, we will use genetic approaches to determine the necessity and sufficiency of BNSTmpm aromatase neurons for social interactions in males and females. In Aim 3, we will use genetically modified mice we have developed to determine the role of aromatase in adult BNSTmpm neurons in the regulation of social interactions. In summary, our proposed studies will provide insight into the neural pathways emanating from aromatase BNSTmpm neurons and their functional relevance in vivo. Health Relatedness: Neurodegenerative and psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The BNST is a critical node linking amygdalar, hypothalamic, and cortical networks in the regulation of social interactions, response to various stressors, and reward pathways. Our proposed studies will shed light on the connectivity and functions of a subset of BNST neurons in the two sexes, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately provide insights into future therapeutic or diagnostic applications for mental illness and common neurodegenerative conditions.