The cerebellum has been implicated in a remarkable number of neurological and neuropsychiatric disorders that range from motoric deficits such as ataxia, tremor, and disequilibrium to autism, schizophrenia, and impulsivity. We do not know why some patients with dysfunction in the cerebellum experience primarily motoric symptoms while others suffer from dysregulated mood and mental health challenges. In this proposal, we examine the specific neural circuits that are responsible for diverse cerebellar motoric and non-motoric dysfunctions. Using a combination of rigorous anatomical methods, including specialized viral circuit tracing vectors that provide new information about brainwide neuronal connections, this research will test the hypothesis that specialized types of cerebellar output neurons are differentially responsible for the diverse disorders associated with the cerebellum. Accomplishments of these experimental goals will generate important new information about the brain- wide connections made by different types of cerebellar output neurons which will enable the development of new diagnostic and therapeutic strategies for patients with a wide range of motoric and neuropsychiatric disorders.
Neurological and neuropsychiatric disorders involve dysyfunctions of interconnected neurons which are widely distributed in many brain regions. Increasing evidence indicates that the cerebellum can improve or restore function after damage or dysregulation in other parts of the brain, but little is known about the specific brainwide circuits that comprise functionally distinct types of cerebellar output neurons. This research project will use rigorous neural circuit connectivity techniques to identify cell- type specific brain-wide connections; the information generated by this research will provide critical missing information for diagnosing and treating neurological and neuropsychiatric disorders.
