Tactile Defensiveness and Impaired Adaptation of Neuronal Activity in the Knock-Out Mouse Model of Autism.

Sensory hypersensitivity is a common symptom in autism spectrum disorders (ASDs), including fragile X syndrome (FXS), and frequently leads to tactile defensiveness. In mouse models of ASDs, there is mounting evidence of neuronal and circuit hyperexcitability in several brain regions, which could contribute to sensory hypersensitivity. However, it is not yet known whether or how sensory stimulation might trigger abnormal sensory processing at the circuit level or abnormal behavioral responses in ASD mouse models, especially during an early developmental time when experience-dependent plasticity shapes such circuits. Using a novel assay, we discovered exaggerated motor responses to whisker stimulation in young knock-out (KO) mice (postnatal days 14-16), a model of FXS. Adult KO mice actively avoided a stimulus that was innocuous to wild-type controls, a sign of tactile defensiveness. Using two-photon calcium imaging of layer 2/3 barrel cortex neurons expressing GCaMP6s, we found no differences between wild-type and KO mice in overall whisker-evoked activity, though 45% fewer neurons in young KO mice responded in a time-locked manner. Notably, we identified a pronounced deficit in neuronal adaptation to repetitive whisker stimulation in both young and adult KO mice. Thus, impaired adaptation in cortical sensory circuits is a potential cause of tactile defensiveness in autism. We use a novel paradigm of repetitive whisker stimulation and calcium imaging to assess tactile defensiveness and barrel cortex activity in young and adult knock-out mice, the mouse model of fragile X syndrome (FXS). We describe evidence of tactile defensiveness, as well as a lack of L2/3 neuronal adaptation in barrel cortex, during whisker stimulation. We propose that a defect in sensory adaptation within local neuronal networks, beginning at a young age and continuing into adulthood, likely contributes to sensory overreactivity in FXS and perhaps other ASDs.