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.

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.

Metrics

  • 3,802
    views
  • 727
    downloads
  • 36
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Share this article

https://doi.org/10.7554/eLife.65502

Further reading

    1. Neuroscience
    Sven Ohl, Martin Rolfs
    Research Article

    Detecting causal relations structures our perception of events in the world. Here, we determined for visual interactions whether generalized (i.e. feature-invariant) or specialized (i.e. feature-selective) visual routines underlie the perception of causality. To this end, we applied a visual adaptation protocol to assess the adaptability of specific features in classical launching events of simple geometric shapes. We asked observers to report whether they observed a launch or a pass in ambiguous test events (i.e. the overlap between two discs varied from trial to trial). After prolonged exposure to causal launch events (the adaptor) defined by a particular set of features (i.e. a particular motion direction, motion speed, or feature conjunction), observers were less likely to see causal launches in subsequent ambiguous test events than before adaptation. Crucially, adaptation was contingent on the causal impression in launches as demonstrated by a lack of adaptation in non-causal control events. We assessed whether this negative aftereffect transfers to test events with a new set of feature values that were not presented during adaptation. Processing in specialized (as opposed to generalized) visual routines predicts that the transfer of visual adaptation depends on the feature similarity of the adaptor and the test event. We show that the negative aftereffects do not transfer to unadapted launch directions but do transfer to launch events of different speeds. Finally, we used colored discs to assign distinct feature-based identities to the launching and the launched stimulus. We found that the adaptation transferred across colors if the test event had the same motion direction as the adaptor. In summary, visual adaptation allowed us to carve out a visual feature space underlying the perception of causality and revealed specialized visual routines that are tuned to a launch’s motion direction.

    1. Neuroscience
    Gergely F Turi, Sasa Teng ... Yueqing Peng
    Research Article

    Synchronous neuronal activity is organized into neuronal oscillations with various frequency and time domains across different brain areas and brain states. For example, hippocampal theta, gamma, and sharp wave oscillations are critical for memory formation and communication between hippocampal subareas and the cortex. In this study, we investigated the neuronal activity of the dentate gyrus (DG) with optical imaging tools during sleep-wake cycles in mice. We found that the activity of major glutamatergic cell populations in the DG is organized into infraslow oscillations (0.01–0.03 Hz) during NREM sleep. Although the DG is considered a sparsely active network during wakefulness, we found that 50% of granule cells and about 25% of mossy cells exhibit increased activity during NREM sleep, compared to that during wakefulness. Further experiments revealed that the infraslow oscillation in the DG was correlated with rhythmic serotonin release during sleep, which oscillates at the same frequency but in an opposite phase. Genetic manipulation of 5-HT receptors revealed that this neuromodulatory regulation is mediated by Htr1a receptors and the knockdown of these receptors leads to memory impairment. Together, our results provide novel mechanistic insights into how the 5-HT system can influence hippocampal activity patterns during sleep.