An integrative assay for measuring social aversion and motivation in freely behaving mice

Social aversion is a key feature of numerous mental health disorders, yet we lack adequate behavioral tools to interrogate social aversion in model systems. Here, we developed a behavioral task-selective access to unrestricted social interaction (SAUSI)-that integrates elements of social motivation, hesitancy, and free interaction to enable a multiplexed assessment of social aversion. Using SAUSI, we discovered that prolonged social isolation induces social aversion in mice-an effect largely driven by increases in social fear coupled with decreases in social motivation. Application of deep learning approaches revealed unique behavioral motifs underlying the socially aversive state produced by isolation, demonstrating the compatibility of modern computational pipelines with SAUSI. Last, we demonstrated that unique forms of social aversion can be induced by distinct stressors, highlighting the versatility of SAUSI. Our findings debut a fresh task for the behavioral toolbox-one that offers an integrative approach for assessing social aversion.