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COUP-TFI regulates diameter of the axon initial segment in the mammalian neocortex

Xuanyuan Wu, Haixiang Li, Jiechang Huang, Cheng Xiao, View ORCID ProfileShuijin He
doi: https://doi.org/10.1101/2020.10.07.329284
Xuanyuan Wu
1School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong New District, Shanghai, 201210, CN
2Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
3University of Chinese Academy of Sciences, Beijing, China
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Haixiang Li
1School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong New District, Shanghai, 201210, CN
2Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
3University of Chinese Academy of Sciences, Beijing, China
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Jiechang Huang
1School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong New District, Shanghai, 201210, CN
2Institute of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China
3University of Chinese Academy of Sciences, Beijing, China
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Cheng Xiao
4School of anesthesiology, Xuzhou Medical University, 209 Tongshan Road, KJL-D423, Xuzhou, Jiangsu Province, 221004, CN
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Shuijin He
1School of Life Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Pudong New District, Shanghai, 201210, CN
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  • ORCID record for Shuijin He
  • For correspondence: heshj@shanghaitech.edu.cn
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Abstract

The axon initial segment is a specialized structure that controls neuronal excitability by generating action potentials. Currently, AIS plasticity with regard to changes in length and location in response to neural activity has been extensively investigated, but how AIS diameter is regulated remains elusive. Here we report that COUP-TFI is an essential regulator of AIS diameter in both developing and adult mouse neocortex. Embryonic ablation of COUP-TFI prevented expansion of AIS diameter that occurs during postnatal development in layer II/III pyramidal cells of the mouse motor cortex, thereby leading to an impairment of action potential generation. Inactivation of COUP-TFI in adult neurons also led to reduced AIS diameter and impaired action potential generation. In contrast to different developmental stages, single-cell ablation and global ablation produced opposite effects on spontaneous network in COUP-TFI-deficient neurons. Further, mice exhibited less anxiety-like behaviors after postnatal inactivation of COUP-TFI induced by tamoxifen. Our results demonstrate that COUP-TFI is indispensable for both expansion and maintenance of AIS diameter and that a change in AIS diameter fine-tunes synaptic inputs through a metaplasticity mechanism in the adult neocortex.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted October 08, 2020.
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COUP-TFI regulates diameter of the axon initial segment in the mammalian neocortex
Xuanyuan Wu, Haixiang Li, Jiechang Huang, Cheng Xiao, Shuijin He
bioRxiv 2020.10.07.329284; doi: https://doi.org/10.1101/2020.10.07.329284
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COUP-TFI regulates diameter of the axon initial segment in the mammalian neocortex
Xuanyuan Wu, Haixiang Li, Jiechang Huang, Cheng Xiao, Shuijin He
bioRxiv 2020.10.07.329284; doi: https://doi.org/10.1101/2020.10.07.329284

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