1. Neuroscience
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The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2

  1. Pierre-Louis Ruffault
  2. Fabien D'Autréaux
  3. John A Hayes
  4. Marc Nomaksteinsky
  5. Sandra Autran
  6. Tomoyuki Fujiyama
  7. Mikio Hoshino
  8. Martin Hägglund
  9. Ole Kiehn
  10. Jean-François Brunet  Is a corresponding author
  11. Gilles Fortin
  12. Christo Goridis
  1. Neuroscience Paris-Saclay Institute, France
  2. Ecole normale supérieure, France
  3. National Institute of Neuroscience, National Center of Neurology and Psychiatry, Japan
  4. Karolinska Institutet, Sweden
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Cite this article as: eLife 2015;4:e07051 doi: 10.7554/eLife.07051

Abstract

Maintaining constant CO2 and H+ concentrations in the arterial blood is critical for life. The principal mechanism through which this is achieved in mammals is the respiratory chemoreflex whose circuitry is still elusive. A candidate element of this circuitry is the retrotrapezoid nucleus (RTN), a collection of neurons at the ventral medullary surface that are activated by increased CO2 or low pH and project to the respiratory rhythm generator. Here, we use intersectional genetic strategies to lesion the RTN neurons defined by Atoh1 and Phox2b expression and to block or activate their synaptic output. Photostimulation of these neurons entrains the respiratory rhythm. Conversely, abrogating expression of Atoh1 or Phox2b or glutamatergic transmission in these cells curtails the phrenic nerve response to low pH in embryonic preparations and abolishes the respiratory chemoreflex in behaving animals. Thus, the RTN neurons expressing Atoh1 and Phox2b are a necessary component of the chemoreflex circuitry.

Article and author information

Author details

  1. Pierre-Louis Ruffault

    Neuroscience Paris-Saclay Institute, Gif sur Yvette, France
    Competing interests
    No competing interests declared.
  2. Fabien D'Autréaux

    Institut de Biologie de l'ENS, Ecole normale supérieure, Paris, France
    Competing interests
    No competing interests declared.
  3. John A Hayes

    Neuroscience Paris-Saclay Institute, Gif sur Yvette, France
    Competing interests
    No competing interests declared.
  4. Marc Nomaksteinsky

    Institut de Biologie de l'ENS, Ecole normale supérieure, Paris, France
    Competing interests
    No competing interests declared.
  5. Sandra Autran

    Neuroscience Paris-Saclay Institute, Gif-sur-Yvette, France
    Competing interests
    No competing interests declared.
  6. Tomoyuki Fujiyama

    Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
    Competing interests
    No competing interests declared.
  7. Mikio Hoshino

    Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan
    Competing interests
    No competing interests declared.
  8. Martin Hägglund

    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  9. Ole Kiehn

    Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    Ole Kiehn, Reviewing editor, eLife.
  10. Jean-François Brunet

    Institut de Biologie de l'ENS, Ecole normale supérieure, Paris, France
    For correspondence
    jfbrunet@biologie.ens.fr
    Competing interests
    No competing interests declared.
  11. Gilles Fortin

    Neuroscience Paris-Saclay Institute, Gif-sur-Yvette, France
    Competing interests
    No competing interests declared.
  12. Christo Goridis

    Institut de Biologie de l'ENS, Ecole normale supérieure, Paris, France
    Competing interests
    No competing interests declared.

Ethics

Animal experimentation: The protocol for this study was approved by the National Committee on the Ethics of Animal Experiments Charles Darwin (Permit Number: Ce5/2012/065).

Reviewing Editor

  1. Marlene Bartos, Albert-Ludwigs-Universität Freiburg, Germany

Publication history

  1. Received: February 17, 2015
  2. Accepted: April 9, 2015
  3. Accepted Manuscript published: April 13, 2015 (version 1)
  4. Version of Record published: May 13, 2015 (version 2)

Copyright

© 2015, Ruffault 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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