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Elife. 2019 Mar 25;8. pii: e41555. doi: 10.7554/eLife.41555.

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

Author information

1
Cellular and Systems Neurobiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, United States.
2
Department of Physics, University of New Hampshire, Durham, United States.
3
Department of Mathematics and Statistics, Georgia State University, Atlanta, United States.
4
Neuroscience Institute, Georgia State University, Atlanta, United States.

Abstract

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.

KEYWORDS:

CAN current; brainstem; computational biology; neuroscience; none; persistent sodium current; respiratory rhythm and pattern; systems biology; transient receptor potential channel

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