Pathology in two brain regions, the cerebellum and frontal cortex, have been commonly reported in autism and other developmental disorders. The relationship between these two abnormalities is unknown. It is likely that autism is, at its essence, a disconnection syndrome that results, at least in part, from a disruption of cerebellar modulation of the prefrontal cortex (PFC). In this study, the researchers will examine mice with cerebellar cell loss to investigate whether cerebellar pathology results in dopaminergic abnormalities in the prefrontal cortex (PFC) and underlies some of the core neuropsychiatric symptomatology of autism. This proposal presents a framework for understanding how these seemingly disparate pathologies are related and provides a unique opportunity for discovery of the neurochemical, electrophysiological and anatomical mechanisms whereby the cerebellum may modulate frontal cortical function, with particular focus on dopamine and Purkinje cell numbers. As the details of the functional interactions and adaptations within this neural circuitry become known, these neural substrates and associated receptor mechanisms should become new candidates for treatment of the cognitive deficits related to autism.