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.
authors: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, Gif-sur-Yvette, France.
authors: Pierre-Louis
authors: PL
authors: Ruffault
authors: Institut de Biologie de l'École Normale Supérieure, Inserm U1024, and CNRS UMR 8197, Paris, France.
authors: Fabien
authors: F
authors: D'Autréaux
authors: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, Gif-sur-Yvette, France.
authors: John A
authors: JA
authors: Hayes
authors: Institut de Biologie de l'École Normale Supérieure, Inserm U1024, and CNRS UMR 8197, Paris, France.
authors: Marc
authors: M
authors: Nomaksteinsky
authors: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, Gif-sur-Yvette, France.
authors: Sandra
authors: S
authors: Autran
authors: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: Tomoyuki
authors: T
authors: Fujiyama
authors: Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: Mikio
authors: M
authors: Hoshino
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Martin
authors: M
authors: Hägglund
authors: Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors: Ole
authors: O
authors: Kiehn
authors: Institut de Biologie de l'École Normale Supérieure, Inserm U1024, and CNRS UMR 8197, Paris, France.
authors: Jean-François
authors: JF
authors: Brunet
authors: Université Paris-Saclay, Université Paris-Sud, CNRS, UMR 9197, Institut des Neurosciences Paris-Saclay, Gif-sur-Yvette, France.
authors: Gilles
authors: G
authors: Fortin
authors: Institut de Biologie de l'École Normale Supérieure, Inserm U1024, and CNRS UMR 8197, Paris, France.
authors: Christo
authors: C
authors: Goridis
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics* / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism / Q000494:pharmacology*; D004622:Embryo, Mammalian; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010775:Photic Stimulation; D010791:Phrenic Nerve / Q000187:drug effects / Q000502:physiology; D011522:Protons; D012119:Respiration / Q000187:drug effects*; D012125:Respiratory Center / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002245:Carbon Dioxide; D018398:Homeodomain Proteins; D011522:Protons; D014157:Transcription Factors; C500943:Atoh1 protein, mouse; C109220:NBPhox protein
keywords: electrophysiology; genetics; hindbrain; mouse; neuroscience; respiration; transcription factors