Altered Cerebellar Response to Somatosensory Stimuli in the Mouse Model of Autism.

Atypical sensory processing is currently included within the diagnostic criteria of autism. The cerebellum is known to integrate sensory inputs of different modalities through its connectivity to the cerebral cortex. Interestingly, cerebellar malformations are among the most replicated features found in postmortem brain of individuals with autism. We studied sensory processing in the cerebellum in a mouse model of autism, knock-out (KO) for the gene. is widely expressed in Purkinje cells (PCs) and has been recently reported to regulate their morphology. Further, individuals with mutations display cerebellar malformations and CNTNAP2 antibodies are associated with a mild form of cerebellar ataxia. Previous studies in the mouse model show an altered cerebellar sensory learning. However, a physiological analysis of cerebellar function has not been performed yet. We studied sensory evoked potentials in cerebellar Crus I/II region on electrical stimulation of the whisker pad in alert mice and found striking differences between wild-type and KO mice. In addition, single-cell recordings identified alterations in both sensory-evoked and spontaneous firing patterns of PCs. These changes were accompanied by altered intrinsic properties and morphologic features of these neurons. Together, these results indicate that the mouse model could provide novel insight into the pathophysiological mechanisms of autism core sensory deficits.