A Novel Head-Fixed Assay for Social Touch in Mice Uncovers Aversive Responses in Two Autism Models

Social touch, an important aspect of social interaction and communication, is essential to kinship across animal species. How animals experience and respond to social touch has not been thoroughly investigated, in part because of the lack of appropriate assays. Previous studies that examined social touch in freely moving rodents lacked the necessary temporal and spatial control over individual touch interactions. We designed a novel head-fixed assay for social touch in mice, in which the experimenter has complete control to elicit highly stereotyped bouts of social touch between two animals. The user determines the number, duration, context, and type of social touch interactions, while monitoring an array of complex behavioral responses with high resolution cameras. We focused on social touch to the face because of its high translational relevance to humans. We validated this assay in two different models of autism spectrum disorder (ASD), the Fmr1 knock-out (KO) model of Fragile X syndrome (FXS) and maternal immune activation (MIA) mice. We observed higher rates of avoidance running, hyperarousal, and aversive facial expressions (AFEs) to social touch than to object touch, in both ASD models compared with controls. Fmr1 KO mice showed more AFEs to mice of the same sex but whether they were stranger or familiar mice mattered less. Because this new social touch assay for head-fixed mice can be used to record neural activity during repeated bouts of social touch it could be used to uncover underlying circuit differences.SIGNIFICANCE STATEMENT Social touch is important for communication in animals and humans. However, it has not been extensively studied and current assays to measure animals' responses to social touch have limitations. We present a novel head-fixed assay to quantify how mice respond to social facial touch with another mouse. We validated this assay in autism mouse models since autistic individuals exhibit differences in social interaction and touch sensitivity. We find that mouse models of autism exhibit more avoidance, hyperarousal, and aversive facial expressions (AFEs) to social touch compared with controls. Thus, this novel assay can be used to investigate behavioral responses to social touch and the underlying brain mechanisms in rodent models of neurodevelopmental conditions, and to evaluate therapeutic responses in preclinical studies.