Aberrant Synaptic Organization in Tremor Disorders

Tremor is a prevalent and often debilitating disorder for many individuals; however, the cause of tremor remains poorly understood. We have previously identified alterations in the cerebellum, the brain region important for motor coordination, in tremor patients. Now, we will study the relationship between this brain pathology and tremor by establishing a mouse model with similar pathological alterations in the cerebellum. We will study tremor characteristics and the alterations of neuronal activities in this novel mouse model, and we will further identify ways that could suppress or enhance tremor by pharmacology and neuromodulation. To further understand how tremor is generated from the abnormal neuronal connections in the brain, we will use novel neuroscience tools to specifically suppress neuronal activities or to disrupt neuronal connections and assess how these manipulations could influence tremor and the abnormal neuronal activities. The results of our proposal will establish a new platform to screen drug therapies for tremor.