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Dbx1 precursor cells are a source of inspiratory XII premotoneurons

  1. Ann L Revill
  2. Nikolas C Vann
  3. Victoria T Akins
  4. Andrew Kottick
  5. Paul A Gray
  6. Christopher A Del Negro
  7. Gregory D Funk  Is a corresponding author
  1. University of Alberta, Canada
  2. The College of William and Mary, United States
  3. Washington University School of Medicine, United States
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Cite this article as: eLife 2015;4:e12301 doi: 10.7554/eLife.12301

Abstract

All behaviors require coordinated activation of motoneurons from central command and premotor networks. The genetic identities of premotoneurons providing behaviorally relevant excitation to any pool of mammalian motoneurons remain unknown. Recently we established in vitro that Dbx1-derived preBötzinger complex neurons are critical for rhythm generation and that a subpopulation serves a premotor function (Wang et al., 2014). Here we further show that a subpopulation of Dbx1-derived intermediate reticular (IRt) neurons are rhythmically active during inspiration and project to the hypoglossal (XII) nucleus that contains motoneurons important for maintaining airway patency. Laser ablation of Dbx1 IRt neurons, 57% of which are glutamatergic, decreased ipsilateral inspiratory motor output without affecting frequency. We conclude that a subset of Dbx1 IRt neurons is a source of premotor excitatory drive, contributing to the inspiratory behavior of XII motoneurons, as well as a key component of the airway control network whose dysfunction contributes to sleep apnea.

Article and author information

Author details

  1. Ann L Revill

    Departments of Physiology, Neuroscience and Mental Health Institute, Women and Children's Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    Competing interests
    The authors declare that no competing interests exist.
  2. Nikolas C Vann

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Victoria T Akins

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Andrew Kottick

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Paul A Gray

    Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Christopher A Del Negro

    Department of Applied Science, The College of William and Mary, Williamsburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Gregory D Funk

    Departments of Physiology, Neuroscience and Mental Health Institute, Women and Children's Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada
    For correspondence
    gf@ualberta.ca
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: Ethics Statement: All experiments were performed in accordance with guidelines laid down by the NIH in the US regarding the care and use of animals for experimental procedures, the Institute for Laboratory Animal Research, and in compliance with protocols approved by the College of William & Mary Institutional Animal Care and Use Committee (protocol #8828), the Animal Studies Committee at Washington University School of Medicine (protocol #20110249) and the University of Alberta of Medicine Animal Welfare Committee (protocol #255).

Reviewing Editor

  1. Ole Kiehn, Karolinska Institutet, Sweden

Publication history

  1. Received: October 14, 2015
  2. Accepted: December 18, 2015
  3. Accepted Manuscript published: December 19, 2015 (version 1)
  4. Version of Record published: February 14, 2016 (version 2)

Copyright

© 2015, Revill 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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