Neuroanatomical Basis of State-Dependent Activity of Upper Airway Muscles

Abstract

Obstructive Sleep Apnea (OSA) is a common sleep-related respiratory disorder that is associated with cognitive, cardiovascular, and metabolic morbidities. The major cause of OSA is the sleep-related reduction of upper airway muscle tone that leads to airway obstructions in individuals with anatomically narrow upper airway. This reduction is mainly due to the suppressant effect of sleep on hypoglossal motoneurons that innervate upper airway muscles. The hypoglossal motoneurons have state-dependent activity, which is decreased during the transition from wakefulness to non-rapid eye movement sleep and is further suppressed during rapid eye movement sleep. Multiple neurotransmitters and their receptors have been implicated in the control of hypoglossal motoneuron activity across the sleep-wake states. However, to date, the results of the rigorous testing show that withdrawal of noradrenergic excitation and cholinergic inhibition essentially contribute to the depression of hypoglossal motoneuron activity during sleep. The present review will focus on origins of noradrenergic and cholinergic innervation of hypoglossal motoneurons and the functional role of these neurons in the state-dependent activity of hypoglossal motoneurons.

Cross‐sectional case‐control study of the relationships between pharyngeal compliance and heart rate variability indices in childhood obstructive sleep apnoea

“…The main results of heart rate variability (HRV) analyses according to the three groups of children and schematic representation of the hypothesis. The upper part of the figure is schematics of brainstem sympathetic nervous system (SNS) and parasympathetic nervous system (PNS: the muscarinic receptors mediate a presynaptic cholinergic inhibition of excitatory glutamatergic transmission to hypoglossal motoneurones) projecting to hypoglossal motoneurones (based on Figure 1 in RukhadzeI & Fenik (2018): left panel: the location of brainstem noradrenergic neurones and cholinergic neurones that project to the hypoglossal nucleus shown on sagittal representation of a rodent brainstem; right panel: a coronal medullary section of a rat brain showing the choline acetyltransferase‐stained motoneurones in the hypoglossal motor nucleus (XII), the dorsal motor nucleus of the vagus (X) and the nucleus of ambiguus, and with part of the paths regulating innervation of the heart), while the lower part (four panels) of the figure is the main results of HRV analyses. Four indices of HRV are described (box and whisker plots show median, 25th and 75th percentiles, and 10th and 90th percentiles); they belong to the oscillatory domain (low frequency/high frequency [LF/HF] ratio), the amplitude domain (HFa and LFa) and the pulse domain (Heart Rate: upper panel).…”

“…Multiple neurotransmitters have been implicated in the control of hypoglossal motoneurone activity across the sleep–wake states. However, withdrawal of noradrenergic excitation and cholinergic inhibition essentially contribute to the depression of hypoglossal motoneurone activity during sleep (RukhadzeI & Fenik, 2018). Active muscarinic inhibition mediates pharyngeal hypotonia, particularly during rapid eye movement (REM) sleep (Grace et al., 2013).…”

Medicinal Marijuana: A Promising Potential Treatment for Obstructive Sleep Apnea

“…In healthy individuals, the airway is kept open by the muscle tone of the genioglossus, palatal, and associated muscles of the throat (3). Those affected by OSA suffer from reduced muscle tone due to suppression of upper airway motoneurons (4). Sleep naturally suppresses these motoneurons, but neuromodulation also plays a role (4).…”

“…Those affected by OSA suffer from reduced muscle tone due to suppression of upper airway motoneurons (4). Sleep naturally suppresses these motoneurons, but neuromodulation also plays a role (4). Common symptoms of individuals suffering from OSA include snoring and silent pauses in breathing (5).…”

Muscarinic Inhibition of Hypoglossal Motoneurons: Possible Implications for Upper Airway Muscle Hypotonia during REM Sleep

“…Hypoglossal motoneurons (HMNs), which control upper airway muscles, are regulated differently than the spinal motor neurons in REM sleep. Work by several groups has concluded that HMNs are inhibited by a combination of monoaminergic disfacilitation and cholinergic inhibition (Horner et al, 2014;Kubin, 2016;Rukhadze and Fenik, 2018).…”