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

View ORCID ProfileMing-Kai Pan ¹,²,³,⁴,⁵,*,
View ORCID ProfileYong-Shi Li⁶,
Shi-Bing Wong⁶,⁷,
View ORCID ProfileChun-Lun Ni⁶,
Yi-Mei Wang⁵,
Wen-Chuan Liu¹,²,
View ORCID ProfileLiang-Yin Lu³,
Jye-Chang Lee⁴,
View ORCID ProfileEtty P. Cortes⁸,
Jean-Paul G. Vonsattel⁸,
View ORCID ProfileQian Sun⁹,¹⁰,
View ORCID ProfileElan D. Louis ¹¹,¹²,
Phyllis L. Faust ⁸ and
View ORCID ProfileSheng-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

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.

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

Yong-Shi Li

6Department of Neurology, Columbia University, New York, NY 10032, USA.

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Shi-Bing Wong

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.

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Chun-Lun Ni

6Department of Neurology, Columbia University, New York, NY 10032, USA.

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Yi-Mei Wang

5Department of Neurology, National Taiwan University Hospital, Yun-Lin Branch, Yun-Lin 64041, Taiwan.

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Wen-Chuan Liu

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.

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Liang-Yin Lu

3Neurobiology and Cognitive Science Center, National Taiwan University, Taipei City 10051, Taiwan.

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Jye-Chang Lee

4Molecular Imaging Center, National Taiwan University, Taipei City 10051, Taiwan.

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Etty P. Cortes

8Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

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Jean-Paul G. Vonsattel

8Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

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Qian Sun

9Department of Neuroscience, Columbia University, New York, NY 10032, USA.

10Department of Neurosciences, Case Western Reserve University, Cleveland, OH 44016, USA.

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Elan D. Louis

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.

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Phyllis L. Faust

8Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.

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Sheng-Han Kuo

6Department of Neurology, Columbia University, New York, NY 10032, USA.

13Initiative 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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