Activity of pontine A7 noradrenergic neurons is suppressed during REM sleep.

The activity of hypoglossal motoneurons plays an important role in the maintenance of upper airway patency. Both withdrawal of noradrenergic excitatory drive and increase of cholinergic inhibition markedly decrease excitability of hypoglossal motoneurons during sleep and especially during rapid-eye-movement (REM) stage. This leads to increased collapsibility of upper airway during sleep, which is the major neurological factor of obstructive sleep apnea (OSA) pathophysiology. Anatomical and functional data suggest that noradrenergic A7 neurons are the main source of noradrenergic drive to hypoglossal motoneurons. However, it is unknown whether the behavior of A7 neurons during sleep-wake cycle is in accord with their proposed involvement in sleep-related depression of hypoglossal motoneuron activity. Therefore, we sought to assess the behavior of A7 neurons during sleep and wakefulness in naturally sleeping head-restrained rats. We have found that, similar to other pontine noradrenergic neurons, the putative A7 noradrenergic neurons fired with relatively long-lasting action potentials with a low-frequency regular discharge. Importantly, noradrenergic A7 neurons were predominantly silent during REM sleep. The REM-off activity of the A7 neurons supports our hypothesis that these neurons may significantly contribute to the withdrawal of excitatory noradrenergic drive from upper airway motoneurons during REM sleep and, consequently, play an essential role in maintaining upper airway patency and pathophysiology of OSA. Therefore, noradrenergic A7 neurons may serve as an additional target for designing pharmacological approaches to treat OSA.NEW & NOTEWORTHY Noradrenergic A7 neurons are mostly silent during REM sleep. This is in accord with their role in the control of upper airway muscles and important contribution to OSA pathophysiology. Therefore, a modulation of A7 neuron activity can serve as a novel therapeutic target for pharmacological treatment of OSA.

Citation

Victor B Fenik, Irma Rukhadze. Activity of pontine A7 noradrenergic neurons is suppressed during REM sleep. Journal of applied physiology (Bethesda, Md. : 1985). 2022 May 26;133(1):130-143

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PMID: 35616303

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