SAUSI: a novel assay for measuring social anxiety and motivation.

Social anxiety is one of the most prevalent mental health disorders, though the underlying neurobiology is poorly understood. Progress in understanding the etiology of social anxiety has been hindered by the lack of comprehensive tools to assess social anxiety in model systems. Here, we created a new behavioral task - Selective Access to Unrestricted Social Interaction (SAUSI), which combines elements of social motivation, hesitancy, decision-making, and free interaction to enable the wholistic assessment of social anxiety-like behaviors in mice. Using this novel assay, we found that social isolation-induced social anxiety-like behaviors in female mice are largely driven by increases in social fear, social hesitancy, and altered ultrasonic vocalizations. Deep learning analyses were able to computationally identify a unique behavioral footprint underlying the state produced by social isolation, demonstrating the compatibility of modern computational approaches with SAUSI. Finally, we compared the results of SAUSI to traditionally social assays including the 3-chamber sociability assay and the resident intruder task. This revealed that behavioral changes induced by isolation were highly context dependent, and that while fragments of social anxiety measured in SAUSI were replicable across other tasks, a wholistic assessment was not obtainable from these alternative assays. 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 anxiety in rodents.