Whole-brain connectivity atlas of glutamatergic and GABAergic neurons in the mouse dorsal and median raphe nuclei

  1. Zhengchao Xu
  2. Zhao Feng
  3. Mengting Zhao
  4. Qingtao Sun
  5. Lei Deng
  6. Xueyan Jia
  7. Tao Jiang
  8. Pan Luo
  9. Wu Chen
  10. Ayizuohere Tudi
  11. Jing Yuan
  12. Xiangning Li
  13. Hui Gong
  14. Qingming Luo
  15. Anan Li  Is a corresponding author
  1. Huazhong University of Science and Technology (HUST), China
  2. HUST-Suzhou Institute for Brainsmatics, China
  3. Hainan University, China

Abstract

The dorsal raphe nucleus (DR) and median raphe nucleus (MR) contain populations of glutamatergic and GABAergic neurons that regulate diverse behavioral functions. However, their whole-brain input-output circuits remain incompletely elucidated. We used viral tracing combined with fluorescence micro-optical sectioning tomography to generate a comprehensive whole-brain atlas of inputs and outputs of glutamatergic and GABAergic neurons in the DR and MR. We found that these neurons received inputs from similar upstream brain regions. The glutamatergic and GABAergic neurons in the same raphe nucleus had divergent projection patterns with differences in critical brain regions. Specifically, MR glutamatergic neurons projected to the lateral habenula through multiple pathways. Correlation and cluster analysis revealed that glutamatergic and GABAergic neurons in the same raphe nucleus received heterogeneous inputs and sent different collateral projections. This connectivity atlas further elucidates the anatomical architecture of the raphe nuclei, which could facilitate better understanding of their behavioral functions.

Data availability

The analysis results and data have been uploaded in the form of Supplementary Table.To present and share the TB-sized raw data, we developed an interactive website (http://atlas.brainsmatics.org/a/xu2011).

Article and author information

Author details

  1. Zhengchao Xu

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  2. Zhao Feng

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  3. Mengting Zhao

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2037-9129
  4. Qingtao Sun

    Biological platform, HUST-Suzhou Institute for Brainsmatics, Suzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  5. Lei Deng

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Xueyan Jia

    Computing platform, HUST-Suzhou Institute for Brainsmatics, Suzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Tao Jiang

    Imaging platform, HUST-Suzhou Institute for Brainsmatics, Suzhou, China
    Competing interests
    The authors declare that no competing interests exist.
  8. Pan Luo

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  9. Wu Chen

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  10. Ayizuohere Tudi

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  11. Jing Yuan

    Britton Chance Center for Biomedical Photonics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9050-4496
  12. Xiangning Li

    Wuhan National Laboratory for Opoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
  13. Hui Gong

    Wuhan National Lab for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5519-6248
  14. Qingming Luo

    School of Biomedical Engineering, Hainan University, Haikou, China
    Competing interests
    The authors declare that no competing interests exist.
  15. Anan Li

    Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology (HUST), Wuhan, China
    For correspondence
    aali@hust.edu.cn
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5877-4813

Funding

National Natural Science Foundation of China (91749209)

  • Qingming Luo

National Natural Science Foundation of China (61890953)

  • Hui Gong

National Natural Science Foundation of China (91827901)

  • Anan Li

Science Fund for Creative Research Groups (61721092)

  • Qingming Luo

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal experiments were approved by the Institutional Animal Care and Use Committee at HUST-Suzhou Institute For Brainsmatics (S20190601) and were conducted in accordance with relevant guidelines.

Reviewing Editor

  1. Hongwei Dong, UCLA, United States

Publication history

  1. Received: December 6, 2020
  2. Preprint posted: December 15, 2020 (view preprint)
  3. Accepted: November 17, 2021
  4. Accepted Manuscript published: November 18, 2021 (version 1)
  5. Version of Record published: November 26, 2021 (version 2)

Copyright

© 2021, Xu et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Zhengchao Xu
  2. Zhao Feng
  3. Mengting Zhao
  4. Qingtao Sun
  5. Lei Deng
  6. Xueyan Jia
  7. Tao Jiang
  8. Pan Luo
  9. Wu Chen
  10. Ayizuohere Tudi
  11. Jing Yuan
  12. Xiangning Li
  13. Hui Gong
  14. Qingming Luo
  15. Anan Li
(2021)
Whole-brain connectivity atlas of glutamatergic and GABAergic neurons in the mouse dorsal and median raphe nuclei
eLife 10:e65502.
https://doi.org/10.7554/eLife.65502

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