High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

Mei-Yu Shi¹, Yuchen Yao², Miao Wang², Qi Yang³, Lufeng Ding⁴, Rui Li³, Yuanyuan Li⁵, Haimeng Huang⁵, Chao-Yu Yang⁶, Zhao Zhou⁷, Zhenxiang Zhu⁸, Pengjie Wen⁹, Fangling Dai¹⁰, Xiaohui Zeng¹⁰, Ke-Ming Zhang¹⁰, Yuhong Guo¹⁰, Zi-An Sun¹⁰, Huanhuan Xia⁶, Zhenhua Ren¹¹, Yusuf Ozgur Cakmak¹², Ming Zhang¹³, Fuqiang Xu¹⁴, Lei Qu¹⁵, Qingyuan Zhu¹⁶, Pak-Ming Lau¹⁷, Cheng Xu¹⁸, Guo-Qiang Bi¹⁹

Affiliations

¹ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China.
² Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, Anhui, China.
³ Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China; Institute of Advanced Technology, University of Science and Technology of China, Hefei 230026, Anhui, China.
⁴ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Bineogen Technology Co., Ltd, Shenzhen 518107, Guangdong, China.
⁵ Ministry of Education Key Laboratory of Intelligent Computation and Signal Processing, Information Materials and Intelligent Sensing Laboratory of Anhui Province, School of Electronics and Information Engineering, Anhui University, Hefei 230601, Anhui, China.
⁶ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
⁷ Anhui Communications Vocational and Technical College, Hefei 230051, Anhui, China.
⁸ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, Hubei, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁹ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
¹⁰ Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China.
¹¹ Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, China.
¹² Department of Anatomy, University of Otago, Dunedin 9054, New Zealand.
¹³ Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; School of Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen 518172, Guangdong, China.
¹⁴ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; University of Chinese Academy of Sciences, Beijing 100049, China.
¹⁵ Ministry of Education Key Laboratory of Intelligent Computation and Signal Processing, Information Materials and Intelligent Sensing Laboratory of Anhui Province, School of Electronics and Information Engineering, Anhui University, Hefei 230601, Anhui, China; SEU-ALLEN Joint Center, Institute for Brain and Intelligence, Southeast University, Nanjing 211189, Jiangsu, China.
¹⁶ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China. Electronic address: qyzhu@ustc.edu.cn.
¹⁷ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China; Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, Anhui, China; The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China. Electronic address: plau@ustc.edu.cn.
¹⁸ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China. Electronic address: xuc@ustc.edu.cn.
¹⁹ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China; Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, Anhui, China; Institute of Advanced Technology, University of Science and Technology of China, Hefei 230026, Anhui, China; The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China. Electronic address: gqbi@ustc.edu.cn.

PMID: 40645171
DOI: 10.1016/j.cell.2025.06.011

Free article

High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

Mei-Yu Shi et al. Cell. 2025.

Free article

. 2025 Jul 10;188(14):3897-3915.e20.

doi: 10.1016/j.cell.2025.06.011.

Authors

Affiliations

¹ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China.
² Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, Anhui, China.
³ Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China; Institute of Advanced Technology, University of Science and Technology of China, Hefei 230026, Anhui, China.
⁴ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Bineogen Technology Co., Ltd, Shenzhen 518107, Guangdong, China.
⁵ Ministry of Education Key Laboratory of Intelligent Computation and Signal Processing, Information Materials and Intelligent Sensing Laboratory of Anhui Province, School of Electronics and Information Engineering, Anhui University, Hefei 230601, Anhui, China.
⁶ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
⁷ Anhui Communications Vocational and Technical College, Hefei 230051, Anhui, China.
⁸ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, Wuhan 430071, Hubei, China; University of Chinese Academy of Sciences, Beijing 100049, China.
⁹ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
¹⁰ Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China.
¹¹ Department of Anatomy, School of Basic Medicine, Anhui Medical University, Hefei 230032, Anhui, China.
¹² Department of Anatomy, University of Otago, Dunedin 9054, New Zealand.
¹³ Department of Anatomy, University of Otago, Dunedin 9054, New Zealand; School of Medicine, The Chinese University of Hong Kong (Shenzhen), Shenzhen 518172, Guangdong, China.
¹⁴ The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; Shenzhen Key Laboratory of Viral Vectors for Biomedicine, NMPA Key Laboratory for Research and Evaluation of Viral Vector Technology in Cell and Gene Therapy Medicinal Products, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China; University of Chinese Academy of Sciences, Beijing 100049, China.
¹⁵ Ministry of Education Key Laboratory of Intelligent Computation and Signal Processing, Information Materials and Intelligent Sensing Laboratory of Anhui Province, School of Electronics and Information Engineering, Anhui University, Hefei 230601, Anhui, China; SEU-ALLEN Joint Center, Institute for Brain and Intelligence, Southeast University, Nanjing 211189, Jiangsu, China.
¹⁶ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China. Electronic address: qyzhu@ustc.edu.cn.
¹⁷ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China; Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, Anhui, China; The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China. Electronic address: plau@ustc.edu.cn.
¹⁸ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China. Electronic address: xuc@ustc.edu.cn.
¹⁹ Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei 230026, Anhui, China; Anhui Province Key Laboratory of Biomedical Imaging and Intelligent Processing, Institute of Artificial Intelligence, Hefei Comprehensive National Science Center, Hefei 230088, Anhui, China; Division of Life Sciences and Medicine, CAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei 230026, Anhui, China; Institute of Advanced Technology, University of Science and Technology of China, Hefei 230026, Anhui, China; The Brain Cognition and Brain Disease Institute, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China. Electronic address: gqbi@ustc.edu.cn.

PMID: 40645171
DOI: 10.1016/j.cell.2025.06.011

Abstract

In contrast to the rapid advancements in mesoscale connectomic mapping of the mammalian brain, similar mapping of the peripheral nervous system has remained challenging due to the body size and complexity. Here, we present a high-speed blockface volumetric imaging system with an optimized workflow of whole-body clearing, capable of imaging the entire adult mouse at micrometer resolution within 40 h. Three-dimensional reconstruction of individual spinal fibers in Thy1-EGFP mice reveals distinct morphological features of sensory and motor projections along the ventral and dorsal rami. Immunostaining facilitates body-wide mapping of sympathetic nerves and their branches, highlighting their perivascular patterns in limb muscles, bones, and most visceral organs. Viral tracing elucidates the fine architecture of vagus nerves and individual vagal fibers, revealing unexpected projection routes to various organs. Our approach offers an effective means to achieve a holistic understanding of cellular-level interactions among different systems that underlie body physiology and disease.

Keywords: VISoR; peripheral nervous system; spinal nerve; sympathetic nerve; tissue clearing; vagus nerve; whole-body imaging.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

Affiliations

High-speed mapping of whole-mouse peripheral nerves at subcellular resolution

Authors

Affiliations

Abstract

Conflict of interest statement

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Full Text Sources

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