ArticleScience translational medicine2020
Cerebellar oscillations driven by synaptic pruning deficits of cerebellar climbing fibers contribute to tremor pathophysiology.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
- The Efficacy and Safety of Transcranial Direct Current Stimulation for Cerebellar Ataxia: a Systematic Review and Meta-Analysis.Cerebellum (London, England) · 2021Pooled it
- Essential Tremor Suppression with a Novel Anti-Tremor Orthosis: A Randomized Crossover Trial.Movement disorders : official journal of the Movement Disorder Society · 2025Trial
- Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study.Annals of clinical and translational neurology · 2024Trial
- Cerebellar rhythms: mechanisms, functions and translational opportunities.Nature reviews. Neuroscience · 2026Review
- Neurophysiological Basis of Tremor Disorders: Parkinson's Disease, Essential Tremor, Tremor in Dystonia, and Holmes Tremor.Seminars in neurology · 2026Review
- Cerebellar neural populations orchestrate dopamine reward signaling with single-trial precision.Nature communications · 2026Article
- Competitive Olivocerebellar Input Selection Promotes Resilient Circuit Formation.bioRxiv : the preprint server for biology · 2026Article
- Compensatory and Dynamic Cerebellar Responses to Striatal Lesions in Experimental Parkinsonism.Cerebellum (London, England) · 2026Article
- Oligodendrocyte Precursor Cells Shape Retinogeniculate Refinement Via a CHD8-Dependent Phagocytic Pathway.Investigative ophthalmology & visual science · 2026Article
- Integrity of Brainstem Connections in Essential Tremor Using Auditory and Vestibular Evoked Potentials.Movement disorders clinical practice · 2026Article
- Tremor pathophysiology.Clinical parkinsonism & related disorders · 2026Review
- A Case of Cala Trio-Induced Glossopharyngeal Neuralgia in a Patient with Essential Tremor and Idiopathic Parkinson's Disease.Tremor and other hyperkinetic movements (New York, N.Y.) · 2026Article
- The cerebellum shapes motions by encoding motor frequencies with precision and cross-individual uniformity.Nature biomedical engineering · 2025Article
- The cerebellar involvement in essential tremor: the connecting roads.Arquivos de neuro-psiquiatria · 2025Review
- Loss-of-function variations in solute carrier family 38 member 6 are associated with essential tremor.Signal transduction and targeted therapy · 2025Article
- Early and widespread cerebellar engagement during hippocampal seizures and interictal discharges.Neurobiology of disease · 2025Article
- Tremor: Clinical Frameworks, Network Dysfunction and Therapeutics.Brain sciences · 2025Review
- Axonal pathology differentially affects human Purkinje cell subpopulations in the essential tremor cerebellum.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cerebello-Prefrontal Connectivity Underlying Cognitive Dysfunction in Spinocerebellar Ataxia Type 2.Annals of clinical and translational neurology · 2025Article
- Oscillatory Coupling Between Thalamus, Cerebellum, and Motor Cortex in Essential Tremor.Movement disorders : official journal of the Movement Disorder Society · 2025Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
Abstract
Essential tremor (ET) is one of the most common movement disorders and the prototypical disorder for abnormal rhythmic movements. However, the pathophysiology of tremor generation in ET remains unclear. Here, we used autoptic cerebral tissue from patients with ET, clinical data, and mouse models to report that synaptic pruning deficits of climbing fiber (CF)-to-Purkinje cell (PC) synapses, which are related to glutamate receptor delta 2 (GluRδ2) protein insufficiency, cause excessive cerebellar oscillations and might be responsible for tremor. The CF-PC synaptic pruning deficits were correlated with the reduction in GluRδ2 expression in the postmortem ET cerebellum. Mice with GluRδ2 insufficiency and CF-PC synaptic pruning deficits develop ET-like tremor that can be suppressed with viral rescue of GluRδ2 protein. Step-by-step optogenetic or pharmacological inhibition of neuronal firing, axonal activity, or synaptic vesicle release confirmed that the activity of the excessive CF-to-PC synapses is required for tremor generation. In vivo electrophysiology in mice showed that excessive cerebellar oscillatory activity is CF dependent and necessary for tremor and optogenetic-driven PC synchronization was sufficient to generate tremor in wild-type animals. Human validation by cerebellar electroencephalography confirmed that excessive cerebellar oscillations also exist in patients with ET. Our findings identify a pathophysiologic contribution to tremor at molecular (GluRδ2), structural (CF-to-PC synapses), physiological (cerebellar oscillations), and behavioral levels (kinetic tremor) that might have clinical applications for treating ET.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.