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Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model

An autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms—a persistent sodium current ([Formula: see text]) and a calcium-activated non-selective cationic curr...

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Autores principales: Phillips, Ryan S, John, Tibin T, Koizumi, Hidehiko, Molkov, Yaroslav I, Smith, Jeffrey C
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433470/
https://www.ncbi.nlm.nih.gov/pubmed/30907727
http://dx.doi.org/10.7554/eLife.41555
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author Phillips, Ryan S
John, Tibin T
Koizumi, Hidehiko
Molkov, Yaroslav I
Smith, Jeffrey C
author_facet Phillips, Ryan S
John, Tibin T
Koizumi, Hidehiko
Molkov, Yaroslav I
Smith, Jeffrey C
author_sort Phillips, Ryan S
collection PubMed
description An autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms—a persistent sodium current ([Formula: see text]) and a calcium-activated non-selective cationic current ([Formula: see text])—were proposed to individually or in combination generate cellular- and circuit-level oscillations, but their roles are debated without resolution. We re-examined these roles in a model of a synaptically connected population of excitatory neurons with [Formula: see text] and [Formula: see text]. This model robustly reproduces experimental data showing that rhythm generation can be independent of [Formula: see text] activation, which determines population activity amplitude. This occurs when [Formula: see text] is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on [Formula: see text] in a subpopulation forming the rhythmogenic kernel. The model explains how the rhythm and amplitude of respiratory oscillations involve distinct biophysical mechanisms.
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spelling pubmed-64334702019-03-27 Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model Phillips, Ryan S John, Tibin T Koizumi, Hidehiko Molkov, Yaroslav I Smith, Jeffrey C eLife Computational and Systems Biology An autorhythmic population of excitatory neurons in the brainstem pre-Bötzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms—a persistent sodium current ([Formula: see text]) and a calcium-activated non-selective cationic current ([Formula: see text])—were proposed to individually or in combination generate cellular- and circuit-level oscillations, but their roles are debated without resolution. We re-examined these roles in a model of a synaptically connected population of excitatory neurons with [Formula: see text] and [Formula: see text]. This model robustly reproduces experimental data showing that rhythm generation can be independent of [Formula: see text] activation, which determines population activity amplitude. This occurs when [Formula: see text] is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on [Formula: see text] in a subpopulation forming the rhythmogenic kernel. The model explains how the rhythm and amplitude of respiratory oscillations involve distinct biophysical mechanisms. eLife Sciences Publications, Ltd 2019-03-25 /pmc/articles/PMC6433470/ /pubmed/30907727 http://dx.doi.org/10.7554/eLife.41555 Text en © 2019, Phillips et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Computational and Systems Biology
Phillips, Ryan S
John, Tibin T
Koizumi, Hidehiko
Molkov, Yaroslav I
Smith, Jeffrey C
Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
title Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
title_full Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
title_fullStr Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
title_full_unstemmed Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
title_short Biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
title_sort biophysical mechanisms in the mammalian respiratory oscillator re-examined with a new data-driven computational model
topic Computational and Systems Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6433470/
https://www.ncbi.nlm.nih.gov/pubmed/30907727
http://dx.doi.org/10.7554/eLife.41555
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