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

Ming-Kai Pan; Yong-Shi Li; Shi-Bing Wong; Chun-Lun Ni; Yi-Mei Wang; Wen-Chuan Liu; Liang-Yin Lu; Jye-Chang Lee; Etty P. Cortes; Jean-Paul G. Vonsattel; Qian Sun; Elan D. Louis; Phyllis L. Faust; Sheng-Han Kuo

doi:10.1126/scitranslmed.aay1769

Research ArticleESSENTIAL TREMOR

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

Ming-Kai Pan ¹,²,³,⁴,⁵,*,
Yong-Shi Li⁶,
Shi-Bing Wong⁶,⁷,
Chun-Lun Ni⁶,
Yi-Mei Wang⁵,
Wen-Chuan Liu¹,²,
Liang-Yin Lu³,
Jye-Chang Lee⁴,
Etty P. Cortes⁸,
Jean-Paul G. Vonsattel⁸,
Qian Sun⁹,¹⁰,
Elan D. Louis ¹¹,¹²,
Phyllis L. Faust ⁸ and
Sheng-Han Kuo ⁶,¹³,*

¹Department of Medical Research, National Taiwan University Hospital, Taipei City 10002, Taiwan.
²Institute of Pharmacology, College of Medicine, National Taiwan University Hospital, Taipei City 10051, Taiwan.
³Neurobiology and Cognitive Science Center, National Taiwan University, Taipei City 10051, Taiwan.
⁴Molecular Imaging Center, National Taiwan University, Taipei City 10051, Taiwan.
⁵Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin 64041, Taiwan.
⁶Department of Neurology, Columbia University, New York, NY 10032, USA.
⁷Department of Pediatrics, Taipei Tzu Chi Hospital, Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.
⁸Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
⁹Department of Neuroscience, Columbia University, New York, NY 10032, USA.
¹⁰Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44016, USA.
¹¹Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT 06519, USA.
¹²Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.
¹³Initiative of Columbia Ataxia and Tremor, New York, NY 10032, USA.

↵*Corresponding author. Email: emorymkpan{at}ntu.edu.tw (M.-K.P.); sk3295{at}columbia.edu (S.-H.K.)

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

Ming-Kai Pan

Department of Medical Research, National Taiwan University Hospital, Taipei City 10002, Taiwan.

Institute of Pharmacology, College of Medicine, National Taiwan University Hospital, Taipei City 10051, Taiwan.

Neurobiology and Cognitive Science Center, National Taiwan University, Taipei City 10051, Taiwan.

Molecular Imaging Center, National Taiwan University, Taipei City 10051, Taiwan.

Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin 64041, Taiwan.

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ORCID record for Ming-Kai Pan
For correspondence: emorymkpan@ntu.edu.tw sk3295@columbia.edu

Yong-Shi Li

Department of Neurology, Columbia University, New York, NY 10032, USA.

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Shi-Bing Wong

Department of Neurology, Columbia University, New York, NY 10032, USA.

Department of Pediatrics, Taipei Tzu Chi Hospital, Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan.

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Chun-Lun Ni

Department of Neurology, Columbia University, New York, NY 10032, USA.

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Yi-Mei Wang

Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin 64041, Taiwan.

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Wen-Chuan Liu

Department of Medical Research, National Taiwan University Hospital, Taipei City 10002, Taiwan.

Institute of Pharmacology, College of Medicine, National Taiwan University Hospital, Taipei City 10051, Taiwan.

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Liang-Yin Lu

Neurobiology and Cognitive Science Center, National Taiwan University, Taipei City 10051, Taiwan.

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Jye-Chang Lee

Molecular Imaging Center, National Taiwan University, Taipei City 10051, Taiwan.

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Etty P. Cortes

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

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Jean-Paul G. Vonsattel

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

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Qian Sun

Department of Neuroscience, Columbia University, New York, NY 10032, USA.

Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44016, USA.

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Elan D. Louis

Department of Neurology, Yale School of Medicine, Yale University, New Haven, CT 06519, USA.

Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA.

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Phyllis L. Faust

Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

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Sheng-Han Kuo

Department of Neurology, Columbia University, New York, NY 10032, USA.

Initiative of Columbia Ataxia and Tremor, New York, NY 10032, USA.

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For correspondence: emorymkpan@ntu.edu.tw sk3295@columbia.edu

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

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