Atypical cortical feedback underlies failure to process contextual information in the superior colliculus of Scn2a^+/-...

Atypical sensory integration and contextual learning are common symptoms in autism spectrum disorder (ASD), but how sensory circuits are affected remains elusive. Here we focused on the early visual information processing, and performed in vivo two-photon calcium imaging and pupillometry of mice engaged in an implicit learning task in stable and volatile visual contexts. Wild-type (WT) mice show stimulus-specific contextual modulation of the visual responses in the superior colliculus (SC) and pupil dynamics, whereas SCN2A-haploinsufficient ASD-model mice exhibit abnormal modulation patterns. In both genotypes, feedforward inputs from the retina to SC demonstrate no such contextual modulation. In contrast, feedback inputs from the primary visual cortex (V1) show modulation patterns similar to those of SC cells in WT mice, but no modulation in Scn2a^+/- mice. Furthermore, chemogenetic perturbation reveals that this top-down signaling from V1 to SC mediates the observed contextual modulation both at the neurophysiological and behavioral levels. These results suggest that the corticotectal input is critical for contextual sensory integration in SC, and its anomaly underlies atypical sensory learning in ASD.