Investigating the role of hippocampocortical circuitry in long term social memory.

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Project Summary Social memory is critical for daily functioning but becomes impaired in many neuropsychiatric disorders, including Alzheimer disease and post-traumatic stress disorder. The dearth of effective therapeutics for social memory deficits demands rigorous study of the neural circuit mechanisms governing social memory dynamics. Recent work in mice has shown that neuronal ensembles in ventral hippocampal area CA1 (vCA1) and medial prefrontal cortex (mPFC) encode various aspects of social interaction, including the identity of a social conspecific. Moreover, intact communication in projections from vCA1 to mPFC is critical for short-term social recognition memory, and mouse models of neuropsychiatric disorders with impaired social memory display corresponding network deficits in this pathway. These findings are well-aligned with a canonical model of long- term memory in which the hippocampus transfers a critical component of a memory’s representation to frontal cortical areas for long-term consolidation. However, mechanisms underlying long-term consolidation of social memories, such as whether social memories abide by this hippocampocortical transfer model, remain largely uninvestigated. A major reason for this deficit is the highly fleeting nature of social memories in common laboratory rodents preventing meaningful efforts to study long-term recall. Thus, the goal of this proposal is to test whether hippocampocortical memory transfer underlies lasting social memory consolidation using a novel model of long-term social memory in pair bonded prairie voles. Prairie voles, like humans, form monogamous, mating-based pair bonds. These bonds require stable, emotionally salient memory of the partner for long-term maintenance; this project will thus leverage pair bonding as a proxy for lasting and emotionally salient social memory. Aim 1 will determine the necessity of intact neuronal signaling in vCA1, mPFC, and vCA1-to-mPFC projections in prairie vole pair bond memory acquisition and long-term recall through reversible chemogenetic inhibition of each circuit component. Aim 2 will examine neuronal dynamics in vCA1 and its projections to mPFC involved in the formation and long-term recall of the memory of a pair bonded partner through in vivo calcium imaging. In sum, this proposal will expand our fundamental understanding of how emotionally salient social memories are formed and stored for distant recall in the brain. This work will also provide the applicant with invaluable training for his future career as a neuropsychiatrist focused on translating foundational knowledge from systems neuroscience into novel, highly precise therapies for cognitive dysfunction.