Research ArticleESSENTIAL TREMOR

Cerebellar oscillations driven by synaptic pruning deficits of cerebellar climbing fibers contribute to tremor pathophysiology

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Science Translational Medicine  15 Jan 2020:
Vol. 12, Issue 526, eaay1769
DOI: 10.1126/scitranslmed.aay1769

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Shake the tremor off

Essential tremor (ET) is a neurological disorder characterized by involuntary rhythmic movements of part of the body. The mechanisms underlying ET development are not completely elucidated. Using autoptic brain tissue, mouse models, and EEG analysis in patients, Pan et al. demonstrated that subjects with ET had excessive cerebellar oscillations that correlated with tremor severity. Mechanistic work showed that the excessive oscillations triggered glutamate receptor delta 2 (GluRδ2) insufficiency and synaptic pruning impairment at climbing fiber–to–Purkinje cell synapses in the cerebellum. Rescuing GluRδ2 reduced cerebellar oscillations and rescued tremor in mice.

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