Brain-wide projection reconstruction of single functionally defined neurons

Meng Wang; Ke Liu; Junxia Pan; Jialin Li; Pei Sun; Yongsheng Zhang; Longhui Li; Wenyan Guo; Qianqian Xin; Zhikai Zhao; Yurong Liu; Zhenqiao Zhou; Jing Lyu; Ting Zheng; Yunyun Han; Chunqing Zhang; Xiang Liao; Shaoqun Zeng; Hongbo Jia; Xiaowei Chen

doi:10.1038/s41467-022-29229-0

Brain-wide projection reconstruction of single functionally defined neurons

Nat Commun. 2022 Mar 22;13(1):1531. doi: 10.1038/s41467-022-29229-0.

Authors

Meng Wang^#^{1

2

3}, Ke Liu^#^{1

2}, Junxia Pan^#^{1

2}, Jialin Li^#³, Pei Sun^#^{1

2}, Yongsheng Zhang^#^{4

5}, Longhui Li^{3

6}, Wenyan Guo^{4

5}, Qianqian Xin^{1

2}, Zhikai Zhao^{1

2}, Yurong Liu^{4

5}, Zhenqiao Zhou⁷, Jing Lyu⁷, Ting Zheng^{4

5}, Yunyun Han⁸, Chunqing Zhang^{1

2}, Xiang Liao⁹, Shaoqun Zeng^{10

11}, Hongbo Jia^{12

13

14

15}, Xiaowei Chen^{16

17

18

19}

Affiliations

¹ Brain Research Center, Third Military Medical University, Chongqing, 400038, China.
² State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, 400038, China.
³ Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing, 400030, China.
⁴ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China.
⁵ MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China.
⁶ Advanced Institute for Brain and Intelligence, Guangxi University, Nanning, 530004, China.
⁷ Brain Research Instrument Innovation Center, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China.
⁸ Department of Neurobiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
⁹ Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing, 400030, China. xiang.liao@cqu.edu.cn.
¹⁰ Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, China. sqzeng@hust.edu.cn.
¹¹ MoE Key Laboratory for Biomedical Photonics, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, China. sqzeng@hust.edu.cn.
¹² Advanced Institute for Brain and Intelligence, Guangxi University, Nanning, 530004, China. jiahb@sibet.ac.cn.
¹³ Brain Research Instrument Innovation Center, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou, 215163, China. jiahb@sibet.ac.cn.
¹⁴ Institute of Neuroscience and the SyNergy Cluster, Technical University Munich, 80802, Munich, Germany. jiahb@sibet.ac.cn.
¹⁵ Combinatorial NeuroImaging Core Facility, Leibniz Institute for Neurobiology, 39118, Magdeburg, Germany. jiahb@sibet.ac.cn.
¹⁶ Brain Research Center, Third Military Medical University, Chongqing, 400038, China. xiaowei_chen@tmmu.edu.cn.
¹⁷ State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing, 400038, China. xiaowei_chen@tmmu.edu.cn.
¹⁸ CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. xiaowei_chen@tmmu.edu.cn.
¹⁹ Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing, 400064, China. xiaowei_chen@tmmu.edu.cn.

^# Contributed equally.

Abstract

Reconstructing axonal projections of single neurons at the whole-brain level is currently a converging goal of the neuroscience community that is fundamental for understanding the logic of information flow in the brain. Thousands of single neurons from different brain regions have recently been morphologically reconstructed, but the corresponding physiological functional features of these reconstructed neurons are unclear. By combining two-photon Ca²⁺ imaging with targeted single-cell plasmid electroporation, we reconstruct the brain-wide morphologies of single neurons that are defined by a sound-evoked response map in the auditory cortices (AUDs) of awake mice. Long-range interhemispheric projections can be reliably labelled via co-injection with an adeno-associated virus, which enables enhanced expression of indicator protein in the targeted neurons. Here we show that this method avoids the randomness and ambiguity of conventional methods of neuronal morphological reconstruction, offering an avenue for developing a precise one-to-one map of neuronal projection patterns and physiological functional features.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Axons
Brain*
Electroporation / methods
Mice
Neurites
Neurons*