Adolescent sleep is critical for the developmental shaping of social novelty preference

Abstract

Sleep takes one-third of our lives, yet its functions remain largely unknown. A large proportion of young patients with neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia have sleep problems, including delayed sleep onset, shortened sleep duration and sleep fragmentation, which have been linked to social interaction deficit, a shared symptom of these disorders. However, the causal relationship between sleep disruption and social defects as well as the underlying mechanisms have not yet been established despite its importance in understanding the etiology of these disorders and developing potential therapeutic means. Here using the three-chamber social interaction test, we found that developmental sleep disruption (SD) in adolescent mice caused significant and long-lasting impairment in the preference towards social novelty during adult social interactions without affecting the overall sociality. Interestingly, SD performed in the adulthood did not induce any social defect, indicating a critical period within adolescence during which sleep shapes social novelty preference. Furthermore, by analyzing the adolescent sleep and adult social behavior in a mouse model of Shank3 mutation that mimics a genetic aberrance in ASDs, we found that the development of sociality is correlated with adolescent NREM sleep while social novelty preference is correlated with adolescent REM sleep. Collectively, these results demonstrate a critical role of adolescent sleep in the forming of social novelty preference and the developmental shaping of social behavior.