Enhanced learning and sensory salience in a cerebellar mouse autism model

Abstract

Among the impairments manifested by autism spectrum disorder (ASD) are sometimes islands of enhanced function1,2. Although neuronal mechanisms for enhanced functions in ASD are unknown, the cerebellum is a major site of developmental alteration, and early-life perturbation to it leads to ASD with higher likelihood than any other brain region3,4. Here we report that a cerebellum-specific transgenic mouse model of ASD shows faster learning on a sensory evidence-accumulation task5. In addition, transgenic mice showed enhanced sensitivity to touch and auditory cues, and prolonged electrophysiological responses in Purkinje-cell complex spikes and associative neocortical regions. These findings were replicated by pairing cues with optogenetic stimulation of Purkinje cells. Computational latent-state analysis of behavior6–8 revealed that both groups of mice with cerebellar perturbations exhibited enhanced focus on current rather than past information, consistent with a role for the cerebellum in retaining information in memory9. We conclude that cerebellar perturbation can activate neocortex via complex spike activity and reduce reliance on prior experience, consistent with a weak-central-coherence account in which ASD traits arise from enhanced detail-oriented processing1. This recasts ASD not so much as a disorder but as a variation that, in particular niches, can be adaptive.