Analyzing the brainstem circuits for respiratory chemosensitivity in freely moving mice

  1. Amol Bhandare
  2. Joseph van de Wiel
  3. Reno Roberts
  4. Inke Braren
  5. Robert Huckstepp
  6. Nicholas Dale  Is a corresponding author
  1. University of Warwick, United Kingdom
  2. University Medical Center Hamburg-Eppendorf, Germany

Abstract

Regulation of systemic PCO2 is a life-preserving homeostatic mechanism. In the medulla oblongata, the retrotrapezoid nucleus (RTN) and rostral medullary Raphe are proposed as CO2 chemosensory nuclei mediating adaptive respiratory changes. Hypercapnia also induces active expiration, an adaptive change thought to be controlled by the lateral parafacial region (pFL). Here we use GCaMP6 expression and head-mounted mini-microscopes to image Ca2+ activity in these nuclei in awake adult mice during hypercapnia. Activity in the pFL supports its role as a homogenous neuronal population that drives active expiration. Our data show that chemosensory responses in the RTN and Raphe differ in their temporal characteristics and sensitivity to CO2, raising the possibility these nuclei act in a coordinated way to generate adaptive ventilatory responses to hypercapnia. Our analysis revises the understanding of chemosensory control in awake adult mouse and paves the way to understanding how breathing is coordinated with complex non-ventilatory behaviours.

Data availability

All data generated or analysed during this study are included in the MS and supporting files. Source data files have been provided for Fig 3D, Fig 7I-K, Fig 1 Supplement 7, and Fig 4 Supplement 2.

Article and author information

Author details

  1. Amol Bhandare

    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Joseph van de Wiel

    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Reno Roberts

    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Inke Braren

    Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Robert Huckstepp

    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4410-3397
  6. Nicholas Dale

    School of Life Sciences, University of Warwick, Coventry, United Kingdom
    For correspondence
    n.e.dale@warwick.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2196-2949

Funding

Medical Research Council (MC_PC_15070)

  • Nicholas Dale

Royal Society

  • Nicholas Dale

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: Experiments were performed in accordance with the European Commission Directive 2010/63/EU (European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes) and the United Kingdom Home Office (Scientific Procedures) Act (1986) with project approval from the University of Warwick's AWERB.

Reviewing Editor

  1. Jeffrey C Smith, National Institute of Neurological Disorders and Stroke, United States

Publication history

  1. Preprint posted: December 10, 2018 (view preprint)
  2. Received: May 25, 2021
  3. Accepted: October 12, 2022
  4. Accepted Manuscript published: October 27, 2022 (version 1)
  5. Version of Record published: November 8, 2022 (version 2)

Copyright

© 2022, Bhandare 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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  1. Amol Bhandare
  2. Joseph van de Wiel
  3. Reno Roberts
  4. Inke Braren
  5. Robert Huckstepp
  6. Nicholas Dale
(2022)
Analyzing the brainstem circuits for respiratory chemosensitivity in freely moving mice
eLife 11:e70671.
https://doi.org/10.7554/eLife.70671
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