Atypical cortical feedback underlies failure to process contextual information in the superior colliculus of Scn2a+/-autism model mice

Abstract

AbstractAtypical sensory integration and contextual learning are common symptoms in autism, but how sensory circuits are affected remains elusive. Here we performedin vivotwo-photon calcium imaging and pupillometry of mice engaged in an implicit learning task in stable and volatile visual contexts. Wild-type and Scn2a-haploinsufficient autism-model mice exhibited distinct patterns of context-dependent modulation in pupil and neuronal dynamics in the superior colliculus, while retinal outputs showed no contextual modulation. A hierarchical Bayesian learning model showed that the superior colliculus largely represented expectations on the task volatility in wild-type mice, but rather on the outcome itself in Scn2a+/-mice, much as suggested in autism. Chemogenetic perturbation revealed that the cortical feedback signals mediated 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 the superior colliculus, and its anomaly underlies abnormal sensory learning in autism.