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Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit

Yuanlei Yue, Pan Xu, Zhichao Liu, Xiaoqian Sun, Juntao Su, Hongfei Du, Lingling Chen, Ryan T. Ash, Stelios Smirnakis, Rahul Simha, Linda Kusner, Chen Zeng, Hui Lu
doi: https://doi.org/10.1101/786822
Yuanlei Yue
1Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA
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Pan Xu
1Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA
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Zhichao Liu
2Department of Physics, Columbian College of Arts and Sciences, The George Washington University, Washington, DC 20037, USA
3Current address: School of Biological Information, Chongqing University of Posts and Telecommunications, Chongqing 400065, China
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Xiaoqian Sun
4Department of Computer Science, School of Engineering and Applied Science, The George Washington University, Washington, DC 20037, USA
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Juntao Su
5Department of Statistics, Columbian College of Arts and Sciences, The George Washington University, Washington, DC 20037, USA
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Hongfei Du
5Department of Statistics, Columbian College of Arts and Sciences, The George Washington University, Washington, DC 20037, USA
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Lingling Chen
1Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA
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Ryan T. Ash
6Department of Psychiatry, Stanford University, Palo Alto, CA 94305, USA
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Stelios Smirnakis
7Department of Neurology, Brigham and Women’s Hospital, Jamaica Plain VA Hospital, Harvard Medical School, Boston, MA 02115, USA
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Rahul Simha
4Department of Computer Science, School of Engineering and Applied Science, The George Washington University, Washington, DC 20037, USA
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Linda Kusner
1Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA
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Chen Zeng
2Department of Physics, Columbian College of Arts and Sciences, The George Washington University, Washington, DC 20037, USA
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Hui Lu
1Department of Pharmacology and Physiology, School of Medicine and Health Sciences, The George Washington University, Washington, DC 20037, USA
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  • For correspondence: huilu@email.gwu.edu
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Abstract

Rett Syndrome (RTT) is a severe neurodevelopmental disorder caused by loss of function of the X-linked Methyl-CpG-binding protein 2 (MECP2). Several case studies report that gross motor function can be improved in children with RTT through treadmill walking, but whether the MeCP2-deficient motor circuit can support actual motor learning remains unclear. We used two-photon calcium imaging to simultaneously observe layer (L) 2/3 and L5a excitatory neuronal activity in the motor cortex (M1) while mice adapted to changing speeds on a computerized running wheel. Despite circuit hypoactivity and weakened functional connectivity across L2/3 and L5a, the Mecp2-null circuit’s firing pattern evolved with improved performance over two weeks. Moreover, trained mice became less anxious and lived 20% longer than untrained mice. Since motor deficits and anxiety are core symptoms of Rett, which is not diagnosed until well after symptom onset, these results underscore the benefit of motor learning.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted August 11, 2021.
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Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit
Yuanlei Yue, Pan Xu, Zhichao Liu, Xiaoqian Sun, Juntao Su, Hongfei Du, Lingling Chen, Ryan T. Ash, Stelios Smirnakis, Rahul Simha, Linda Kusner, Chen Zeng, Hui Lu
bioRxiv 786822; doi: https://doi.org/10.1101/786822
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Motor training improves coordination and anxiety in symptomatic Mecp2-null mice despite impaired functional connectivity within the motor circuit
Yuanlei Yue, Pan Xu, Zhichao Liu, Xiaoqian Sun, Juntao Su, Hongfei Du, Lingling Chen, Ryan T. Ash, Stelios Smirnakis, Rahul Simha, Linda Kusner, Chen Zeng, Hui Lu
bioRxiv 786822; doi: https://doi.org/10.1101/786822

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