Wednesday, April 2, 2025
4/2/2025
Decoding the specificity of social drives - ABSTRACT Social behaviors consist of a flexible seeking-approach phase followed by a social action phase. While decades of elegant work have described specific subcortical circuits necessary for the execution of distinct social actions (e.g. aggression and mating), the extent to which various nodes in the social brain network encode specific social drives has been largely unexplored. Understanding this question will provide essential insight into how the brain generates motivated states for specific social actions, which are essential both for both survival and general well-being. The ventrolateral area (VMHvl) is one brain region that has been shown to play an essential role in various social actions such as aggression and mating. Recent evidence suggests neural activity in this region specifically generates and maintains aggressive-motivation states. However, whether this encoding is specific for aggression, or represents a more generalized socially motivated state, is unknown. Here, we will test the specific hypothesis that the VMHvl encodes signatures of motivation that are specific to desired future social actions, against the alternative hypothesis, that social drive is generalized, and invariant to future social action. To do this, I will employ a novel two-choice social operant paradigm which allows animals to freely switch between seeking access for male or female social rewards. I will use this task along with state-of-the art high- density neural recordings, activity-dependent tagging methods, functional perturbation experiments, and single-nucleus RNA sequencing (snRNAseq) for a multiplexed analysis of VMHvl encoding of distinct social drives. First, I will perform in vivo electrophysiological recordings to determine if and when social choices can be predicted from VMHvl neural activity. Next, I will take advantage of a novel activity dependent tagging methods to drive gene expression in VMHvl neurons active during disparate socially motivated states. Using this tagging method to drive expression of opsins or fluorescent reporters, I test the functional specificity of VMHvl neurons activated during distinct social drives and perform molecular profiling of these cells. Together, this proposal combines multiple powerful techniques to yield new insights about the computational, functional, and molecular specificity of a evolutionarily conserved hypothalamic node in generating specific social drives.
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