Journal
ELIFE
Volume 8, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.41555
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Funding
- Jayne Koskinas Ted Giovanis Foundation for Health and Policy
- National Institute of Neurological Disorders and Stroke Intramural Research Program of the National Institutes of Health
- National Institutes of Health [R01 AT008632, U01 EB021960]
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [ZIANS003108, ZIANS002899] Funding Source: NIH RePORTER
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An autorhythmic population of excitatory neurons in the brainstem pre-Botzinger complex is a critical component of the mammalian respiratory oscillator. Two intrinsic neuronal biophysical mechanisms-a persistent sodium current (I-NaP) and a calcium-activated non-selective cationic current (I-CAN)-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 I-CAN and I-NaP. This model robustly reproduces experimental data showing that rhythm generation can be independent of I-CAN activation, which determines population activity amplitude. This occurs when I-CAN is primarily activated by neuronal calcium fluxes driven by synaptic mechanisms. Rhythm depends critically on I-NaP 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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