Dbx1 precursor cells are a source of inspiratory XII premotoneurons

Author:

Revill Ann L1ORCID,Vann Nikolas C2ORCID,Akins Victoria T2ORCID,Kottick Andrew2ORCID,Gray Paul A3,Del Negro Christopher A2ORCID,Funk Gregory D1ORCID

Affiliation:

1. Department of Physiology, Neuroscience and Mental Health Institute, Women and Children's Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada

2. Department of Applied Science, The College of William and Mary, Williamsburg, United States

3. Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, United States

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 respiratory motoneurons remain unknown. Recently, we established in vitro that Dbx1-derived pre-Bötzinger complex neurons are critical for rhythm generation and that a subpopulation serves a premotor function (<xref ref-type="bibr" rid="bib50">Wang et al., 2014</xref>). 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.

Funder

National Heart, Lung, and Blood Institute

Canadian Institutes of Health Research

Natural Sciences and Engineering Research Council of Canada

Alberta Innovates - Health Solutions

Canada Foundation for Innovation

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

Reference52 articles.

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