Cortico-amydala circuit dysfunction underlying avoidance behaviors and aversive facial expressions to social touch in mouse models of autism

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PROJECT ABSTRACT Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by deficits in social interaction, repetitive behaviors and atypical sensory processing. The change in quality of life in ASD individuals is primarily attributed to social deficits, which can be associated with (or even triggered by) atypical processing of sensory information. In particular, social touch deficits in ASD may explain this association given the strong relationship between social interaction deficits and tactile hypersensitivity in ASD. Early tactile hyperresponsivity predicts future social impairments in ASD children and the absence of touch prevents ASD children from forming social relationships as adults. ASD individuals also lack representations of affective social touch in somatosensory brain regions. In mouse models of ASD, tactile sensitivity and social touch interactions also appear to be linked. Still, several important questions about social touch remain unresolved. First, it is not known when social touch behavioral deficits first emerge in ASD. These deficits may emerge early on in development when sensory hypersensitivity first develops or later in adolescence when social experiences become more frequent. Second, little is known about how social touch and maladaptive behaviors to social touch are represented in the brain of ASD individuals. Relevant brain areas may include the primary somatosensory cortex (S1), which encodes social touch and shows impaired adaptation to innocuous tactile stimuli in ASD mouse models, and the basolateral amygdala (BLA), which is important for encoding aversive stimuli and salient social information. To investigate social touch deficits in mouse models of autism, I have designed a novel head-fixed behavioral assay during which behavioral responses to social touch can be measured. This assay allows me to spatially and temporally control social touch interactions between mice so that I can assess the behavioral responses to both voluntary (whisker-whisker contact) and forced (snout-snout contact) social touch in a test mouse as it interacts with a stranger mouse. My preliminary data already shows that both the Fragile X Syndrome and maternal immune activation mouse models of autism animals display increased avoidance behaviors and aversive facial expressions (AFEs) to both voluntary and forced social touch compared to their controls in adulthood. Furthermore, these maladaptive behaviors are more prominent during social touch than object touch. For this proposal, I will utilize this novel behavioral assay and in vivo silicon probe electrophysiology recordings (Neuropixels) to 1. investigate when avoidance behaviors and AFEs to social touch emerge during development (postnatal and juvenile ages) in ASD mice and 2. determine how social touch and the maladaptive behavioral responses it triggers in ASD are represented as neural dynamics in S1 and BLA. This proposal is significant because it will provide the first characterization of behavioral manifestations of social touch deficits across development and investigate the neural circuit disruptions underlying these deficits in mouse models of ASD.