Grammer Jordan, Valles Rene, Bowles Alexis, Zelikowsky Moriel
Department of Neurobiology, University of Utah, United States.
bioRxiv. 2024 Dec 7:2024.05.13.594023. doi: 10.1101/2024.05.13.594023.
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.
社交厌恶是众多心理健康障碍的关键特征，如社交焦虑症和自闭症谱系障碍。然而，社交厌恶背后的生物行为机制仍知之甚少。由于缺乏在模型系统中评估社交厌恶的综合工具，在理解社交厌恶病因方面的进展受到了阻碍。在此，我们创建了一项新的行为任务——选择性进入无限制社交互动（SAUSI），该任务整合了社交动机、犹豫、决策和自由互动等要素，以全面评估小鼠的社交厌恶。使用这种新颖的检测方法，我们发现社交隔离诱导的小鼠社交厌恶在很大程度上是由社交恐惧和社交动机的增加所驱动的。深度学习分析揭示了隔离产生的社交厌恶状态背后独特的行为特征，证明了现代计算方法与SAUSI的兼容性。我们还使用传统检测方法进一步评估了社交厌恶，包括三室社交性检测和常驻入侵者检测，这些方法足以揭示社交厌恶表型的片段，包括社交动机或社交互动的变化，但未能对社交厌恶进行全面评估。至关重要的是，这些检测方法不足以揭示社交厌恶的关键组成部分，包括社交冻结和社交犹豫行为。最后，我们证明了SAUSI具有通用性，因为它可用于评估由非社会应激源（如足部电击）诱导的社交厌恶。我们的研究结果为行为工具箱引入了一项新任务——该任务克服了先前检测方法的局限性，允许进行社交选择以及自由互动，并为评估啮齿动物的社交厌恶提供了一种新方法。
