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Inhibitory control of excitatory networks contributes to cortical functions. Increasing evidence indicates that parvalbumin (PV+)-expressing basket cells (BCs) are a major player in maintaining the balance between excitation (E) and inhibition (I). Disruption of E/I balance in cortical networks is believed to be a hallmark of autism spectrum disorder (ASD). Here, we report a lateralized decrease in the number of PV +  BCs in L2/3 of the somatosensory cortex in the dominant hemisphere of Shank3 −/−  and Cntnap2 −/−  mouse models of ASD. The dominant hemisphere was identified during a reaching task to establish each animal’s dominant forepaw. Double labeling with anti-PV antibody and a biotinylated lectin ( Vicia villosa  lectin [VVA]) showed that the number of BCs was not different but rather, some BCs did not express PV (PV − ), resulting in an elevated number of PV −  VVA+ BCs. Finally, we showed that dominant hindpaws had higher mechanical sensitivity when compared with the other hindpaws. This mechanical hypersensitivity in the dominant paw strongly correlated with the decrease in the number of PV +  interneurons and reduced PV expression in the corresponding cortex. Together, these results suggest that the hypersensitivity in ASD patients could be due to decreased inhibitory inputs to the dominant somatosensory cortex.

Lateralized Decrease of Parvalbumin + Cells in the Somatosensory Cortex of ASD Models Is Correlated with Unilateral Tactile Hypersensitivity