Project Summary Early life sleep is fundamental to the development of affiliative behavior, defined as any behavioral display that promotes positive social engagement. Autism spectrum disorder (ASD) is characterized by persistent changes in social behavior, sensory sensitivity, and sleep disruption. Additionally, excitatory, and inhibitory neuronal activity (E/I balance) is altered in ASD. Increased expression of parvalbumin-positive inhibitory interneurons and the appearance of extracellular structures, perineuronal nets (PNNs) surrounding these cells mark the functional maturation of the sensory cortex. The highly social prairie vole is an excellent model with which to study the relationship between early-life sleep and the development of neural circuitry underlying the display of affiliative behavior. Unlike mice and rats, prairie voles demonstrate species-typical familiarity preference demonstrated by side-by-side huddling in a novel environment. Our lab has shown early-life sleep disruption (ELSD) in prairie voles impairs species-typical affiliative behavior (huddling) and increases PV interneurons (PVIs) in the somatosensory cortex of adults. However, we do not know how ELSD impacts the early display of affiliative behavior nor how PV interneurons may mediate this early behavioral development. Our understanding of social behavior has been largely limited to manual scoring using a fixed set of identifiers. Use of novel computational tools for the objective discovery of affiliative behavior will allow for a more comprehensive understanding of subtle cues in this complex behavior during development. Thus, I propose to investigate the development of affiliative behavior between same-sex siblings (Aim 1) and PVIs (Aim 2) of male and female prairie voles across adolescence (P28-42) following ELSD (P14-21) or the Control condition. Characterizing the trajectory of both brain and behavior is expected to provide key insights into the functional role of early-life sleep in social development. The central hypothesis of this work is that, early-life sleep disruption alters the maturation of PV interneurons and results in reduced affiliative behavior between siblings during development. To understand the mechanisms underlying the timing of PV expression and affiliative behavior, we will randomize animals to standard housing versus an enriched environment (Aim 3) to probe potential rescue of brain and behavioral changes induced by ELSD. Identifying the molecular trajectories by which ELSD changes typical affiliative behavior and how enrichment modifies these social impairments may enable a better understanding of mechanisms underlying successful therapies for children with ASD.