Studying how the hippocampal-prefrontal-hypothalamic circuit encodes social dominance

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Project Summary Social deficits are common in psychiatric disorders and available treatments are limited. Our lack of basic knowledge on how the brain controls social behaviors makes it challenging to develop therapeutics for social deficits. For numerous animal species, social rank dictates many aspects of behavior, such as access to resources and resilience to stress. Individuals with higher social rank typically win more often during social conflicts (e.g. food competition) and show more agonistic behaviors; collectivity referred to as dominance behaviors. Cross-species evidence suggests that the medial prefrontal cortex (mPFC) plays an important role in social dominance. However, exactly how the mPFC encodes social rank and which mPFC inputs and outputs contribute to dominance behaviors is unknown. Multiple studies show that the ventral hippocampus (vHPC) is necessary for social memory, and more recently, a study showed that this role involves vHPC input to the mPFC. Furthermore, preliminary data suggest that the projection from the mPFC to the lateral hypothalamus (LH) modulates social dominance behavior. These findings in combination with the literature suggest a model in which the mPFC receives social memory information from the vHPC and guides social behaviors via modulation of LH GABAergic and glutamatergic subpopulations. Progress in uncovering neural correlates of social behavior has been limited by the tools used to characterize murine social behavior, since existing social assays lack trial- structure needed for statistical power and common measurements of social behavior are simplistic (e.g. sniffing). Overcoming this challenge required developing a trial-based social competition assay in which mice compete against cagemates for a reward signaled by a tone. Due to its trial structure, this assay facilitates the quantification of social behaviors and subsequently the identification of neural correlates for social dominance. In this assay, dominant mice win most of the rewards across trials, occupy the reward port and displace mice from the reward port more often than subordinates. Machine learning approaches will be used to profile the behavioral differences seen across social rank during the competition assay. Utilizing this ethologically relevant social competition assay, circuit manipulations, in vivo neural recording methods and machine learning allows testing the hypothesis that the tripartite vHPC-mPFC-LH circuit encodes social dominance. Altogether, this research will provide a new approach to study social dominance and will further our understanding of how the distributed circuits of the mPFC modulate social behavior. Furthermore, pinpointing the neural circuits underlying social behaviors will facilitate identification of potential therapeutics for social deficits in psychiatric disorders. Finally, completion of this research will provide training opportunities in statistical approaches for behavioral analysis and new circuit dissection tools, which are essential for the candidate to become an expert in social neuroscience and to start a successful independent research program.