The Cerebellar Involvement in Autism Spectrum Disorders: From the Social Brain to Mouse Models

Autism spectrum disorders (ASD) are pervasive neurodevelopmental disorders that include a variety of forms and clinical phenotypes. This heterogeneity complicates the clinical and experimental approaches to ASD etiology and pathophysiology. To date, a unifying theory of these diseases is still missing. Nevertheless, the intense work of researchers and clinicians in the last decades has identified some ASD hallmarks and the primary brain areas involved. Not surprisingly, the areas that are part of the so-called "social brain", and those strictly connected to them, were found to be crucial, such as the prefrontal cortex, amygdala, hippocampus, limbic system, and dopaminergic pathways. With the recent acknowledgment of the cerebellar contribution to cognitive functions and the social brain, its involvement in ASD has become unmistakable, though its extent is still to be elucidated. In most cases, significant advances were made possible by recent technological developments in structural/functional assessment of the human brain and by using mouse models of ASD. Mouse models are an invaluable tool to get insights into the molecular and cellular counterparts of the disease, acting on the specific genetic background generating ASD-like phenotype. Given the multifaceted nature of ASD and related studies, it is often difficult to navigate the literature and limit the huge content to specific questions. This review fulfills the need for an organized, clear, and state-of-the-art perspective on cerebellar involvement in ASD, from its connections to the social brain areas (which are the primary sites of ASD impairments) to the use of monogenic mouse models.