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

Pierre Louis Ruffault; Fabien D’Autréaux; John A. Hayes; Marc Nomaksteinsky; Sandra Autran; Tomoyuki Fujiyama; Mikio Hoshino; Martin Hägglund; Ole Kiehn; Jean François Brunet; Gilles Fortin; Christo Goridis

doi:10.7554/elife.07051

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

Pierre Louis Ruffault, Fabien D’Autréaux, John A. Hayes, Marc Nomaksteinsky, Sandra Autran, Tomoyuki Fujiyama, Mikio Hoshino, Martin Hägglund, Ole Kiehn, Jean François Brunet, Gilles Fortin^*, Christo Goridis

^*Corresponding author for this work

49 Citations (Scopus)

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.

Original language	English
Article number	e07051
Journal	eLife
Volume	2015
Issue number	4
ISSN	2050-084X
DOIs	https://doi.org/10.7554/elife.07051
Publication status	Published - 13 Apr 2015
Externally published	Yes

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title = "The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2",

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.",

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T1 - The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO2

AU - Ruffault, Pierre Louis

AU - D’Autréaux, Fabien

AU - Hayes, John A.

AU - Nomaksteinsky, Marc

AU - Autran, Sandra

AU - Fujiyama, Tomoyuki

AU - Hoshino, Mikio

AU - Hägglund, Martin

AU - Kiehn, Ole

AU - Brunet, Jean François

AU - Fortin, Gilles

AU - Goridis, Christo

PY - 2015/4/13

Y1 - 2015/4/13

N2 - 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.

AB - 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.

U2 - 10.7554/elife.07051

DO - 10.7554/elife.07051

M3 - Journal article

C2 - 25866925

AN - SCOPUS:84928152032

SN - 2050-084X

VL - 2015

JO - eLife

JF - eLife

IS - 4

M1 - e07051

ER -

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

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