Dbx1 precursor cells are a source of inspiratory XII premotoneurons

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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.

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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.
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.
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.
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.
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.
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.
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).

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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.