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.
Article and author information
Author details
Reviewing Editor
- Marlene Bartos, Albert-Ludwigs-Universität Freiburg, Germany
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).
Version history
- Received: February 17, 2015
- Accepted: April 9, 2015
- Accepted Manuscript published: April 13, 2015 (version 1)
- 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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