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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.

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


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.


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

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