Social peers rescue autism‐relevant sociability deficits in adolescent mice

Abstract

Lay AbstractLimited reciprocal social interactions are central to the diagnosis of autism. Behavioral intervention programs are effective in improving social and communication skills in children with autism. We are employing mouse models to understand the individual components of behavioral interventions which effectively improve social interactions. BTBR T+tf/J (BTBR) is an inbred strain of mice that exhibits multiple social deficits, unusual vocalizations, and high levels of repetitive behaviors, which are relevant to all three diagnostic symptom categories of autism. C57BL/6J (B6) is an inbred strain of mice that exhibits high sociability and low repetitive behaviors. We reasoned that these mouse strains with low versus high social interactions might be useful for evaluating social peer enrichment as a behavioral intervention during adolescence. Juvenile BTBR and B6 of the same sex were placed in a same home cage and lived together as cagemates until they reached young adulthood. The two control groups were juvenile B6 housed together, and juvenile BTBR housed together. B6 controls that lived with B6 cagemates showed their strain-typical high sociability. BTBR controls that lived with BTBR cagemates showed their strain-typical low sociability. Remarkably, BTBR that shared home cages with B6 showed high sociability as young adults. Peer rearing for either 20 days or 40 days were equally effective. These results from a robust mouse model of autism support the strategy of early behavioral intervention for treating the social domain in autism spectrum disorders, including beneficial interactions with social peers. Scientific AbstractBehavioral therapies are currently the most effective interventions for treating the diagnostic symptoms of autism. We employed a mouse model of autism to evaluate components of behavioral interventions that improve sociability in mice. BTBR T+tf/J (BTBR) is an inbred mouse strain that exhibits prominent behavioral phenotypes with face validity to all three diagnostic symptom categories of autism, including robust and well-replicated deficits in social approach and reciprocal social interactions. To investigate the role of peer interactions in the development of sociability, BTBR juvenile mice were reared in the same home cage with juvenile mice of a highly social inbred strain, C57BL/6J (B6). Subject mice were tested as young adults for sociability and repetitive behaviors. B6 controls reared with B6 showed their strain-typical high sociability. BTBR controls reared with BTBR cagemates showed their strain-typical lack of sociability. In contrast, BTBR reared with B6 as juveniles showed significant sociability as young adults. A 20-day intervention was as effective as a 40-day intervention for improving social approach behavior. High levels of repetitive self-grooming by BTBR were not rescued by peer- rearing with B6, indicating specificity of the intervention to the social domain. These results from a robust mouse model of autism support the interpretation that social enric...

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