Encoding social arousal within prepronociceptin circuits in the extended amygdala

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TITLE Encoding social arousal within prepronociceptin circuits in the extended amygdala PROJECT SUMMARY/ABSTRACT As a social species, humans thrive on the ability to form social connections for individual well-being, survival, and societal success. Physiological arousal responses regulate this process by encoding information from social stimuli that guides subsequent behavioral actions. Dysregulation of the neural circuitry responsible for encoding arousal responses is thought to contribute to disturbed motivated behavior, a characteristic in many neuropsychiatric disorders. We can track the rapid changes in arousal responses by recording certain physiological metrics such as pupil size, frequency of heartbeats, and respiratory cycles, however, little is known about the neural circuits that regulate these rapid arousal responses and how they influence ongoing social behavior. We recently found that neurons that express the prepronociceptin gene in the BNST (BNSTPnoc neurons) encode the arousal responses that occur rapidly upon exposure to motivationally salient stimuli, such as predator and food odors. Interestingly, BNSTPnoc neurons project predominantly to the medial amygdala (MeA) and the medial preoptic area (mPOA), which are brain regions that regulate aspects of social motivation. Here, we will study how BNSTPnoc neurons that project to either MeA or mPOA regulate social arousal responses and modulate social behaviors. Our global hypothesis is that unique populations of BNSTPnoc neurons will selectively encode arousal responses to social stimuli in a stimulus-dependent manner and independent of encoding behavior. To accomplish this, we will precisely map afferent and efferent circuit connections of BNSTPnoc neurons (Aim 1), test the hypothesis that BNSTPnoc neurons encode social arousal responses (Aim 2), and test the hypothesis that neurons that encode arousal responses influence social behaviors (Aim 3). Identifying the function and natural dynamics of BNSTPnoc neurons is important because we currently do not understand the role of arousal in the generation of behavior and behavioral disorders, nor do we understand the circuitry underlying the contributions of arousal on social behavior. This gap in knowledge prevents us from developing therapeutic strategies that target this potentially critical biological substrate to treat disorders defined by maladaptive social behaviors.