1. Neuroscience
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PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate

  1. Clément Menuet  Is a corresponding author
  2. Angela A Connelly
  3. Jaspreet K Bassi
  4. Mariana R Melo
  5. Sheng Le
  6. Jessica Kamar
  7. Natasha N Kumar
  8. Stuart J McDougall
  9. Simon McMullan
  10. Andrew M Allen  Is a corresponding author
  1. Institut de Neurobiologie de la Méditerranée, France
  2. University of Melbourne, Australia
  3. Macquarie University, Australia
  4. University of New South Wales, Australia
  5. Florey Institute of Neuroscience and Mental Health, Australia
Research Article
  • Cited 9
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Cite this article as: eLife 2020;9:e57288 doi: 10.7554/eLife.57288

Abstract

Heart rate and blood pressure oscillate in phase with respiratory activity. A component of these oscillations is generated centrally, with respiratory neurons entraining the activity of pre-sympathetic and parasympathetic cardiovascular neurons. Using a combination of optogenetic inhibition and excitation in vivo and in situ in rats, as well as neuronal tracing, we demonstrate that preBötzinger Complex (preBötC) neurons, which form the kernel for inspiratory rhythm generation, directly modulate cardiovascular activity. Specifically, inhibitory preBötC neurons modulate cardiac parasympathetic neuron activity whilst excitatory preBötC neurons modulate sympathetic vasomotor neuron activity, generating heart rate and blood pressure oscillations in phase with respiration. Our data reveal yet more functions entrained to the activity of the preBötC, with a role in generating cardiorespiratory oscillations. The findings have implications for cardiovascular pathologies, such as hypertension and heart failure, where respiratory entrainment of heart rate is diminished and respiratory entrainment of blood pressure exaggerated.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. Source data and statistics files have been provided for Figures 2, 3, 4, 5, 6, 7 and 8.

Article and author information

Author details

  1. Clément Menuet

    INSERM U1249, Institut de Neurobiologie de la Méditerranée, Marseille, France
    For correspondence
    clement.menuet@inserm.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7419-6427
  2. Angela A Connelly

    Department of Physiology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  3. Jaspreet K Bassi

    Department of Physiology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  4. Mariana R Melo

    Department of Physiology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  5. Sheng Le

    Faculty of Medicine & Health Sciences, Macquarie University, Macquarie University, Australia
    Competing interests
    The authors declare that no competing interests exist.
  6. Jessica Kamar

    Department of Physiology, University of Melbourne, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
  7. Natasha N Kumar

    Department of Pharmacology, University of New South Wales, Sydney, Australia
    Competing interests
    The authors declare that no competing interests exist.
  8. Stuart J McDougall

    Systems Neurophysiology, Florey Institute of Neuroscience and Mental Health, Parkville, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8778-675X
  9. Simon McMullan

    Faculty of Medicine & Health Sciences, Macquarie University, Macquarie University, Australia
    Competing interests
    The authors declare that no competing interests exist.
  10. Andrew M Allen

    Department of Physiology, University of Melbourne, Parkville, Australia
    For correspondence
    a.allen@unimelb.edu.au
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2183-5360

Funding

National Health and Medical Research Council (App #1120477)

  • Clément Menuet
  • Simon McMullan
  • Andrew M Allen

National Health and Medical Research Council (App #1156727)

  • Clément Menuet
  • Simon McMullan
  • Andrew M Allen

Australian Research Council (DP120100920)

  • Simon McMullan
  • Andrew M Allen

Australian Research Council (DP170104582)

  • Andrew M Allen

University of Melbourne (-McKenzie Research Fellowship)

  • Clément Menuet

Fondation pour la Recherche Médicale (Fellowship ARF20160936221)

  • Clément Menuet

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

Ethics

Animal experimentation: Experiments were conducted in accordance with the Australian National Health and Medical Research Council 'Code of Practice for the Care and Use of Animals for Scientific Purposes' and were approved by the University of Melbourne Animal Research Ethics and Biosafety Committees (ethics ID #1413273, #1614009, #1814599 and Florey 16-040).

Reviewing Editor

  1. Muriel Thoby-Brisson, CNRS Université de Bordeaux, France

Publication history

  1. Received: March 26, 2020
  2. Accepted: June 14, 2020
  3. Accepted Manuscript published: June 15, 2020 (version 1)
  4. Version of Record published: June 30, 2020 (version 2)

Copyright

© 2020, Menuet 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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