UCLA

Sensory overreactivity 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 new behavioral assay, we discovered exaggerated motor responses to whisker stimulation in young Fmr1-/- mice (postnatal days (P) 14-16), a model of FXS. Adult Fmr1-/- mice actively avoided the same stimulus, a sign of tactile defensiveness. Using a novel protocol for expressing and imaging GCaMP6s in L2/3 barrel cortex neurons of early postnatal mice, we found no differences between wild-type and Fmr1-/- mice in overall whisker-evoked activity, though 45% fewer neurons in young Fmr1-/- 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 Fmr1-/- mice. Thus, impaired adaptation in cortical sensory circuits is a potential cause of tactile defensiveness in autism.