Laser ablation of Dbx1 neurons in the pre-Bötzinger Complex stops inspiratory rhythm and impairs output in neonatal mice
- Massachusetts General Hospital, United States
- The College of William and Mary, United States
- University of Alberta, Canada
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.
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Animal experimentation: The Institutional Animal Care and Use Committee (IACUC) at The College of William & Mary, which ensures compliance with United States federal regulations concerning care and use of vertebrate animals in research, approved the following protocols (IACUC-2013-07-10-8828-cadeln). The anesthesia and surgery protocols are consistent with the 2011 guidelines of the Animal Research Advisory Committee, which is part of the Office of Animal Care and Use of the National Institutes of Health of the USA.
Copyright
© 2014, Wang 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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Laser ablation of Dbx1 neurons in the pre-Bötzinger Complex stops inspiratory rhythm and impairs output in neonatal mice
eLife 3:e03427.
https://doi.org/10.7554/eLife.03427
