Brain mechanisms underlying how social stimuli elicit motivated behavior - ABSTRACT Neural mechanisms underlying emotional processing and motivated behavior have historically been most studied using stimuli devoid of social content. However, stimuli communicating social information also drive motivated behavior and emotions. For example, when a subject interacts with a member of their social cohort, motivated behavior and emotional responses can differ depending upon the hierarchical rank of the subject and of the group member encountered. This grant strives to understand where and how neural representations of social information converge onto neural circuitry known to mediate motivated behavior and emotional responses. The proposal targets the anterior cingulate cortex (ACC)-basolateral amygdala (BLA) interconnected circuit with the goal of understanding how representations of social rank gain access to circuits driving motivated behavior. Recent studies have shown that the BLA and ACC both contain neurons that respond more strongly to either dominant or submissive social stimuli. These areas also contain neurons that represent reward values. In rodents, ACC has been shown to help maintain social hierarchy during competitive tasks between mice of different ranks, and physiological evidence suggests that the same neural ensembles in the amygdala can represent the motivational significance of social and non-social stimuli. Our approach studies social groups of mice exhibiting stable hierarchies. Leveraging the fact that olfaction is the dominant sensory modality in rodents, we assess how urine sample odors from dominant and submissive mice influence the motivated behavior of intermediate-ranked mice. We use two behavioral assays of motivated behavior: 1) a nose poke assay in which we measure the degree to which dominant and submissive urine odors elicit approach behavior, a simple and paradigmatic motivated behavior, and 2) a urine preference test, in which two urine odors from dominant and submissive mice are presented simultaneously, just like multiple social stimuli are often present simultaneously in naturalistic settings. Mice can freely choose to approach or avoid either odor. We take a 3 pronged approach to understand the BLA-ACC circuit in mediating the studied motivated behavior: 1) we elucidate physiological response properties in relation to social odors driving motivated behavior in both tasks (Aim 1); 2) we determine the necessity of neural activity of BLA input to ACC, and ACC input to BLA, during motivated behavior elicited by social odors, and trace the sensory input into the ACC and BLA neurons that provide input to the other structure (Aim 2); and 3) we manipulate the activity of dominant or submissive preferring neurons in BLA and ACC to test if they modulate motivated behavior in both tasks, and determine if dominant or submissive preferring neurons in BLA have direct projections to ACC, and vice-versa for ACC neurons. These studies promise to pave the way for future studies that extend the focus of study to 1) neural circuit elements beyond ACC and BLA important for transforming sensory representations of social stimuli to motivated behavior, and 2) genetic mouse models of psychiatric disorders that are characterized by social and emotional dysfunction.
