title: Dbx1 precursor cells are a source of inspiratory XII premotoneurons.
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 (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.
authors.affiliation: 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.
authors.forename: Ann L
authors.identifier: http://orcid.org/0000-0002-6071-6866
authors.initials: AL
authors.lastname: Revill
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: Nikolas C
authors.identifier: http://orcid.org/0000-0003-4139-0642
authors.initials: NC
authors.lastname: Vann
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: Victoria T
authors.identifier: http://orcid.org/0000-0002-0061-7612
authors.initials: VT
authors.lastname: Akins
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: Andrew
authors.identifier: http://orcid.org/0000-0002-3731-5140
authors.initials: A
authors.lastname: Kottick
authors.affiliation: Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, United States.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Gray
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: Christopher A
authors.identifier: http://orcid.org/0000-0002-7848-8224
authors.initials: CA
authors.lastname: Del Negro
authors.affiliation: 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.
authors.forename: Gregory D
authors.identifier: http://orcid.org/0000-0001-5848-0631
authors.initials: GD
authors.lastname: Funk
mesh_terms: D000200:Action Potentials; D000818:Animals; D005260:Female; D018398:Homeodomain Proteins / Q000032:analysis*; D007002:Hypoglossal Nerve / Q000502:physiology*; D001239:Inhalation / Q000502:physiology*; D051379:Mice; D009046:Motor Neurons / Q000502:physiology*
chemical_list: C103403:Dbx1 protein, mouse; D018398:Homeodomain Proteins
keywords: brainstem; breathing; central pattern generator; motor behavior; mouse; neuroscience