Purkinje cell misfiring generates high-amplitude action tremors that are corrected by cerebellar deep brain stimulation

eLife

Joshua J White¹  Tao Lin¹  Roy V Sillitoe²  Meike E van der Heijden²  Amanda M Brown³  Joy Zhou³ 

[1] Department of Neuroscience, Baylor College of Medicine, Houston, United States;Jan and Dan Duncan Neurological Research Institute of Texas Children's Hospital, Houston, United States;Department of Pathology and Immunology, Baylor College of Medicine, Houston, United States;

关键词: tremor;    cerebellum;    purkinje;    optogenetics;    electrophysiology;    deep brain stimulation;   

DOI  :  10.7554/eLife.51928

来源: DOAJ

【 摘 要 】

Tremor is currently ranked as the most common movement disorder. The brain regions and neural signals that initiate the debilitating shakiness of different body parts remain unclear. Here, we found that genetically silencing cerebellar Purkinje cell output blocked tremor in mice that were given the tremorgenic drug harmaline. We show in awake behaving mice that the onset of tremor is coincident with rhythmic Purkinje cell firing, which alters the activity of their target cerebellar nuclei cells. We mimic the tremorgenic action of the drug with optogenetics and present evidence that highly patterned Purkinje cell activity drives a powerful tremor in otherwise normal mice. Modulating the altered activity with deep brain stimulation directed to the Purkinje cell output in the cerebellar nuclei reduced tremor in freely moving mice. Together, the data implicate Purkinje cell connectivity as a neural substrate for tremor and a gateway for signals that mediate the disease.

【 授权许可】

Unknown