Optogenetic Interrogation of Cerebellar Circuitry of a Novel Mouse Model of Essential Tremor

Here’s an overview of a 2018 Research Study which received grant funding from the IETF:

Principal Investigator: Sheng-Han Kuo, MD,
Columbia University

The major obstacle for the effective therapy development for essential tremor is the unclear brain structural alterations that leads to tremor. To overcome this obstacle, we have previously identified structural alterations in the cerebellum, the brain region important for motor coordination, in essential tremor patients. Now, we will determine how this brain pathology can lead to tremor by establishing a mouse model with similar pathological alterations in the cerebellum. We will use the novel neuroscience tools to specifically silence the neuronal activities within the cerebellum in this mouse model and we will assess how these manipulations can influence tremor. The results of our proposal will establish a new platform to screen therapies for essential tremor and will advance our knowledge of essential tremor.

AIM 1: Identify the role of PC (Purkinje cell) activities in tremor.
AIM 2: Identify the essential role of CF (climbing fiber) activities in tremor.
AIM 3: Identify the essential role of CF-PC synaptic transmission in tremor.

IMPACT: The completion of the aims will establish an important mouse model for ET, which will have a high translational impact for preclinical development of ET therapy and will also advance our knowledge of synaptic organization in tremor.