1. The retrotrapezoid nucleus neurons expressing Atoh1 and Phox2b are essential for the respiratory response to CO₂.
- Author
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Ruffault PL, D'Autréaux F, Hayes JA, Nomaksteinsky M, Autran S, Fujiyama T, Hoshino M, Hägglund M, Kiehn O, Brunet JF, Fortin G, and Goridis C
- Subjects
- Animals, Basic Helix-Loop-Helix Transcription Factors metabolism, Carbon Dioxide metabolism, Embryo, Mammalian, Gene Expression, Homeodomain Proteins metabolism, Hydrogen-Ion Concentration, Membrane Potentials drug effects, Membrane Potentials physiology, Mice, Mice, Transgenic, Neurons cytology, Neurons metabolism, Photic Stimulation, Phrenic Nerve drug effects, Phrenic Nerve physiology, Protons, Respiratory Center cytology, Respiratory Center metabolism, Synapses drug effects, Synapses physiology, Synaptic Transmission drug effects, Synaptic Transmission physiology, Transcription Factors metabolism, Basic Helix-Loop-Helix Transcription Factors genetics, Carbon Dioxide pharmacology, Homeodomain Proteins genetics, Neurons drug effects, Respiration drug effects, Respiratory Center drug effects, Transcription Factors genetics
- 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.
- Published
- 2015
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