title: Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice.
abstract: To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality. Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors. Here, we show that selective photonic destruction of Dbx1 preBötC neurons in neonatal mouse slices impairs respiratory rhythm but surprisingly also the magnitude of motor output; respiratory hypoglossal nerve discharge decreased and its frequency steadily diminished until rhythm stopped irreversibly after 85±20 (mean ± SEM) cellular ablations, which corresponds to ∼15% of the estimated population. These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations. We also establish quantitative cellular parameters that govern network viability, which may have ramifications for respiratory pathology in disease states.
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: Xueying
authors.identifier: http://orcid.org/0000-0002-2399-8083
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: John A
authors.identifier: http://orcid.org/0000-0003-2849-7672
authors.initials: JA
authors.lastname: Hayes
authors.affiliation: Department of Physiology, University of Alberta, Edmonton, Canada The Women and Children's Health Research Institute, 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: Hanbing
authors.identifier: http://orcid.org/0000-0002-2164-8813
authors.initials: H
authors.lastname: Song
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 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 Biology, The College of William and Mary, Williamsburg, United States.
authors.forename: M Drew
authors.identifier: http://orcid.org/0000-0002-4037-1848
authors.initials: MD
authors.lastname: LaMar
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.
authors.forename: Maria Cristina D
authors.identifier: http://orcid.org/0000-0001-8912-2175
authors.initials: MC
authors.lastname: Picardo
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 Physiology, University of Alberta, Edmonton, Canada The Women and Children's Health Research Institute, University of Alberta, Edmonton, Canada.
authors.forename: Gregory D
authors.identifier: http://orcid.org/0000-0001-5848-0631
authors.initials: GD
authors.lastname: Funk
authors.affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States cadeln@wm.edu.
authors.forename: Christopher A
authors.identifier: http://orcid.org/0000-0002-7848-8224
authors.initials: CA
authors.lastname: Del Negro
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D015870:Gene Expression; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D007002:Hypoglossal Nerve / Q000503:physiopathology*; D001239:Inhalation / Q000502:physiology; D007395:Interneurons / Q000166:cytology / Q000502:physiology; D053685:Laser Therapy; D051379:Mice; D008822:Mice, Transgenic; D009046:Motor Neurons / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D012125:Respiratory Center / Q000293:injuries / Q000473:pathology / Q000503:physiopathology*; D056152:Respiratory Rate; D046509:Tissue Culture Techniques
chemical_list: C103403:Dbx1 protein, mouse; D018398:Homeodomain Proteins
keywords: breathing; central pattern generator; preBötzinger complex; respiration; two-photon microscopy