SAUSI: an integrative assay for measuring social aversion and motivation.

Social aversion is a key feature of numerous mental health disorders such as Social Anxiety and Autism Spectrum Disorders. Nevertheless, the biobehavioral mechanisms underlying social aversion remain poorly understood. Progress in understanding the etiology of social aversion has been hindered by the lack of comprehensive tools to assess social aversion in model systems. Here, we created a new behavioral task - Selective Access to Unrestricted Social Interaction (SAUSI), which integrates elements of social motivation, hesitancy, decision-making, and free interaction to enable the wholistic assessment of social aversion in mice. Using this novel assay, we found that social isolation-induced social aversion in mice is largely driven by increases in social fear and social motivation. Deep learning analyses revealed a unique behavioral footprint underlying the socially aversive state produced by isolation, demonstrating the compatibility of modern computational approaches with SAUSI. Social aversion was further assessed using traditional assays - including the 3-chamber sociability assay and the resident intruder assay - which were sufficient to reveal fragments of a social aversion phenotype, including changes to either social motivation or social interaction, but which failed to provide a wholistic assessment of social aversion. Critically, these assays were not sufficient to reveal key components of social aversion, including social freezing and social hesitancy behaviors. Lastly, we demonstrated that SAUSI is generalizable, as it can be used to assess social aversion induced by non-social stressors, such as foot shock. Our findings debut a novel task for the behavioral toolbox - one which overcomes limitations of previous assays, allowing for both social choice as well as free interaction, and offers a new approach for assessing social aversion in rodents.