Autism spectrum disorders (ASDs) are prevalent neurodevelopmental disorders characterized by repetitive behaviors and impairments in social interaction. Recent studies have implicated the cerebellum and cerebellar circuits in the pathogenesis of ASD. Peter Tsai and colleagues have recently generated a model to examine the impact of cerebellar dysfunction on ASD behaviors. Using this cerebellar mouse model of tuberous sclerosis complex (TSC), a neurodevelopmental disorder associated with high rates of ASD, Tsai and colleagues have demonstrated that cerebellar dysfunction is sufficient to generate ASD-like behaviors in mice. Moreover, they have demonstrated that early treatment of the TSC molecular signaling deficit resulted in the rescue of pathology and behavioral disruption in these mice¹. However, whether these findings are generalizable to other ASD models remains to be examined. In addition, how cerebellar dysfunction results in ASD behaviors, the specific cerebellar domains that regulate ASD behaviors and the therapeutic benefits of targeted neuromodulation remain unknown.

To address these questions, Tsai and his team have generated preliminary data implicating cerebellar function in ASD behaviors. Tsai’s team proposes to identify the generalizability of these findings and to identify the specific cerebellar substrates mediating these behaviors. To do so, the team will use both cerebellar-specific and cerebellar-agnostic models of ASD. Moreover, they propose to delineate the therapeutic benefits of cerebellar neuromodulation for the treatment of ASD-related behaviors. These proposed studies will establish the contribution of the cerebellum to ASD and provide pre-clinical evidence for cerebellar neuromodulation as a translational strategy for the treatment of ASD-related behaviors.