Cerebellum and Mental Disorders

Abstract The cerebellum has been implicated in a number of mental health disorders such as autism spectrum disorder (ASD), schizophrenia, and addiction. However, how it contributes to these disorders is not understood. In this proposal we explore whether the cerebellum sends direct excitatory projections to the ventral tegmental area (VTA), one of the brain regions that processes and encodes reward, and to the hypothalamus, a region implicated in social behavior. Using a combination of anatomical, functional (electrophysiology combined with selective optogenetic activation of cerebellar pathways), and behavioral studies we test the hypothesis that direct cerebellar projections to these two brain structures may be the substrate through which the cerebellum influences social behavior under physiological and pathological conditions. Defects in cerebellar modulation of the VTA and hypothalamus may explain, at least in part, how the cerebellum might contribute to disorders such as ASD and schizophrenia. Thus, accomplishment of the goals set would not only advance our understanding of the non-motor functions of the cerebellum, but may provide clues regarding the pathophysiology of a number of mental disorders.