A critical role for the murine anterior insula in male social avoidance after early life maltreatment.

Maltreatment in children and adolescents poses a major public health crisis as a primary factor for the development of adult psychiatric disorders. However effective treatments for symptoms resulting from early life maltreatment are lacking, in part due to a lack of understanding of how neural circuits are disrupted in adulthood after childhood and adolescent abuse. We used a novel model of developmental maltreatment (early adolescent chronic social defeat stress, eaCSDS) in C57/B6J mice to examine behavioral and circuit-level effects in the adult anterior insula (AI). We combined chemogenetics, whole brain c-fos imaging and multi-site LFP to investigate the role of the AI and related circuitry in adult behavioral dysfunction after early life maltreatment. Behavioral analysis in adult animals reveals that males, but not females, show robust generalized social avoidance after social defeat in early adolescence. Chemogenetic silencing of AI neurons in males, but not females, reduces social avoidance in adulthood after eaCSDS. In males, whole brain c-fos imaging and multi-site LFP recordings further reveal circuit-level disruptions in connectivity to AI, implicating AI dysregulation as a driver of adult male social avoidance after adolescent maltreatment. Together these findings reveal AI as a novel circuits-level target whose activity normalization may reduce fear-based symptoms of adolescent maltreatment in adulthood specifically in males.