Cell-type and projection-specific dissection of the bed nucleus of the stria terminalis in the mediation of social behavioral deficits induced by early life adversity

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PROJECT SUMMARY Nearly one percent of children in the US experience childhood abuse or neglect, which can induce life-long behavioral deficits including social behavior disorders like social anxiety, attachment disorders, difficult peer relations, and externalizing behaviors. Investigations into the neural mechanisms mediating early life adversity induced behavioral impairments have largely focused on dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and its release of the stress hormone corticotropin-releasing factor (CRF), which accounts for aspects of altered anxiety and responsiveness to stress induced by early life adversity. However, social interaction involves coordination between neural circuits promoting reward and circuits inhibiting anxiety, and thus neural substrates mediating early life adversity-induced social deficits likely extend beyond HPA axis dysfunction, but this has not been systematically investigated. Our parent grant is designed to address the extent to which early adversity-induced social deficits are driven by dysfunction in anxiety versus reward circuits, critical for effectively treating disorders spurred by childhood abuse and neglect. Our lab uses mouse maternal separation with early weaning (MSEW) to model early life adversity, which robustly reduces social interaction and increases anxiety-like behavior, recapitulating effects of childhood abuse and neglect. Prior findings in my and others’ labs have consistently shown that rodent maternal separation procedures adversely affect females to a greater extent than males. This mirrors the human clinical population, as females exhibit greater rates of anxiety-related disorders and depression than males. While research for the parent grant considers sex as an experimental factor, we have devised a study to further examine how exposure to early life adversity interferes with the development of sexually dimorphic neuronal systems to permanently alter behavior. Ms. Janet Ronquillo will carry out this experimentation during a post-baccalaureate gap year, during which she will also follow a rigorous plan to set her up for success in her future career path.