Impact of juvenile social isolation on maturation of frontal circuit and SUD-relevant behavior

Early life social experiences, especially social deprivation, can have long-lasting consequences on risk for developing psychiatric disorders including Substance Use Disorders (SUD). Animal studies have also shown that juvenile social isolation (jSI) dysregulates adult social and cognitive behaviors relevant to SUD. However, how early isolation alters the developmental trajectory of circuits and behaviors implicated in SUD is poorly understood. Our long-term goal is to elucidate neural mechanisms mediating the impact of jSI on neurobehavioral development and the risk for SUD in adolescence and adulthood. Among many brain regions, prefrontal cortex (PFC), which provides top-down control to sub-cortical areas essential for reward processing, has been extensively implicated to be dysregulated in SUD. it is hypothesized that jSI dysregulates adolescent reciprocal social interaction, which leads to an imbalance between the two types of subcortically projecting mPFC neurons, ultimately contributing to SUD-relevant cognitive behavior deficits. This project will conduct the preparative activities at the behavioral (Aim1) and circuit level (Aim2) that are essential to establish feasibility and validity to test the aforementioned hypothesis. To this end we will form an interdisciplinary team with expertise in developmental psychobiology, circuit manipulation/measurement, behavioral electrophysiology, machine learning-based behavioral analysis, and SUD-related cognitive behavior in rodent models, as well as expertise in human developmental psychology and human SUD-related developmental imaging studies. These preparatory activities will set a stage for a future project to conduct multimodal longitudinal study using rat models to examine the impact of juvenile social isolation on PFC circuit maturation, social play trajectory, and adult SUD related behavior.