Cerebello-cortical Network and Parkinson’s Disease

Orateur : Fabien MENARDY (ENS Paris)

In Parkinson’s disease, midbrain dopaminergic neuron degeneration leads to major functional changes in the basal ganglia-thalamo-cortical and cerebello-thalamo-cortical pathways in patients. The consequences of the alterations of the cerebello-thalamo-cortical pathways have been less studied in this disease. We combine pharmacological manipulations, in vivo electrophysiological recordings, and optogenetic stimulation in transgenic mice expressing ChR2 in Purkinje cells to assess the functional connectivity in the cerebello-cortical pathway and the contribution of the cerebellum to the motor impairments in Parkinson’s disease and in dyskinesia, a side effect induced by the levodopa treatment in the late phase of the disease. Our experiments reveal major changes in the cerebello-cortical pathway in an animal model of Parkinson’s disease, with a paradoxical inhibitory influence of the cerebellum on the motor cortex. In parallel, cerebellar stimulations decreased the disabling involuntary movements in levodopa-induced dyskinesia. Overall, these results demonstrate that the cerebellum contributes to the functional alterations observed in Parkinson’s disease.

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