Mechanisms of experience-dependent plasticity in an innate social behavior circuit

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Project Summary Many social behaviors, such as defense and aggression, are innate- requiring no prior experience to be expressed and presumably ‘hardwired’ into neural circuits. Interestingly, however, these ‘hardwired’ behaviors vary in expression among individuals and can be altered by experience. What are the neural circuits and mechanisms that support such flexible expression of innate behaviors? The ventrolateral, ventromedial hypothalamus (VMHvl) controls innate social behaviors including aggression and social defense, but whether VMHvl encodes individual differences in the expression of these behaviors, or how VMHvl may mediate experience-dependent behavioral changes is not understood. An experience that exposes individual differences in innate behavior and induces experience-dependent changes to aggression and defense behavior is chronic social defeat stress (CDS). CDS induces persistent changes to VMHvl activity- but the cell- types, circuits, and mechanisms involved in these transformations are unidentified. This proposal will use CDS to produce a range of social behavior decisions and dissect the cell-types, circuits, and synaptic mechanisms that mediate these decisions using multiple levels of analysis. This includes in-vivo imaging of individual neurons to characterize the activity dynamics of VMHvl throughout the course of CDS, electrophysiological recordings to uncover the cellular and synaptic signatures of CDS in VMHvl circuits, and in-vivo optogenetic manipulation during behavior to perturb VMHvl CDS-plasticity. This proposal constitutes significant technical and conceptual training in circuit-mapping, in-vivo recordings, in-vivo circuit manipulation, cell-type and input- specific synaptic plasticity, and computational and quantitative methods of analysis. Together, completion of this research will elucidate the experience-dependent transformations to VMHvl circuit dynamics that occur throughout social stress, and relate these transformations to individual differences in stress outcome. Examining these relationships will provide insight to the mechanisms underlying stress-plasticity, which provide insight to stress-related mental health disorders.