Linking dynamics of the inhibitory network to the input structure

Komarov, Maxim; Bazhenov, Maxim

doi:10.1007/s10827-016-0622-8

Cited by 3 publications

(2 citation statements)

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“…Since there are no direct recordings from IPI and EPI, we used a canonical model of spiking neuron with spike frequency adaptation (Colbert and Pan 2002;Mainen and Sejnowski 1996;Traub 1982). The membrane potential of each neuron was governed by the following equation (Komarov and Bazhenov 2016):…”

Section: Models For Individual Neuron Dynamicsmentioning

confidence: 99%

Computational model of brain-stem circuit for state-dependent control of hypoglossal motoneurons

Naji

Komarov

Malhotra

et al. 2018

Journal of Neurophysiology

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In patients with obstructive sleep apnea (OSA), the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Experimental studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contributes to depression of hypoglossal motoneurons and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. In this new study, we developed a biophysical network model to test the hypothesis that, to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons needs to include excitatory and inhibitory perihypoglossal interneurons that mediate noradrenergic and serotonergic drives to hypoglossal motoneurons. In the model, the state-dependent activation of the hypoglossal motoneurons was in qualitative agreement with in vivo data during simulated rapid eye movement (REM) and non-REM sleep. The model was applied to test the mechanisms of action of noradrenergic and serotonergic drugs during REM sleep as observed in vivo. We conclude that the proposed minimal neuronal circuit is sufficient to explain in vivo data and supports the hypothesis that perihypoglossal interneurons may mediate state-dependent monoaminergic drive to hypoglossal motoneurons. The population of the hypothesized perihypoglossal interneurons may serve as novel targets for pharmacological treatment of OSA. NEW & NOTEWORTHY In vivo studies suggest that during rapid eye movement sleep, withdrawal of noradrenergic and serotonergic drives critically contributes to depression of hypoglossal motoneurons (HMs), which innervate the tongue muscles. By means of a biophysical model, which is consistent with a broad range of empirical data, we demonstrate that the neuronal network controlling the excitability of HMs needs to include excitatory and inhibitory interneurons that mediate noradrenergic and serotonergic drives to HMs.

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Section: Models For Individual Neuron Dynamicsmentioning

confidence: 99%

Computational model of brain-stem circuit for state-dependent control of hypoglossal motoneurons

Naji

Komarov

Malhotra

et al. 2018

Journal of Neurophysiology

Self Cite

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“…The populations of the IPI and EPI were modeled using Hodgkin-Huxley formalism. The membrane potential of each neuron was governed by the following equation (Kilpatrick and Ermentrout 2011;Komarov and Bazhenov 2016;Traub 1982):…”

Section: Models For Individual Neuron Dynamicsmentioning

confidence: 99%

Computational model of brainstem circuit for state-dependent control of hypoglossal motoneurons

Naji

Komarov

Malhotra

et al. 2017

Preprint

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In patients with obstructive sleep apnea (OSA) the pharyngeal muscles become relaxed during sleep, which leads to a partial or complete closure of upper airway. Empirical studies suggest that withdrawal of noradrenergic and serotonergic drives importantly contribute to depression of hypoglossal motoneurons during rapid eye-movement (REM) sleep and, therefore, may contribute to OSA pathophysiology; however, specific cellular and synaptic mechanisms remain unknown. It was recently suggested that, in order to explain experimental observations, the neuronal network for monoaminergic control of excitability of hypoglossal motoneurons has to include excitatory and inhibitory perihypoglossal interneurons that would mediate noradrenergic and serotonergic drives to the motoneurons. In this study, we applied a biophysical network model to validate the rationality of the proposed circuit and to investigate the dynamics of its neuronal populations during REM sleep-induced withdrawal of noradrenergic and serotonergic drives. The state-dependent activity of the model hypoglossal motoneurons during simulated REM sleep with or without a virtual application of noradrenergic and serotonergic drugs was in qualitative agreement with in vivo data. The study predicts the dynamics of the perihypoglossal interneurons during these conditions and corroborates the hypothesis that the excitatory interneurons may integrate both noradrenergic and serotonergic drives. The latter drive has to be mediated by the inhibitory interneurons. The study suggests that perihypoglossal interneurons may serve as novel potential targets for pharmacological treatment of OSA.

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