Revisiting Antagonist Effects in Hypoglossal Nucleus: Brainstem Circuit for the State-Dependent Control of Hypoglossal Motoneurons: A Hypothesis

We reassessed and provided new insights into the findings that were obtained in our previous experiments that employed the injections of combined adrenergic, serotonergic, GABAergic, and glycinergic antagonists into the hypoglossal nucleus in order to pharmacologically abolish the depression of hypoglossal nerve activity that occurred during carbachol-induced rapid-eye-movement (REM) sleep-like state in anesthetized rats. We concluded that noradrenergic disfacilitation is the major mechanism that is responsible for approximately 90% of the depression of hypoglossal motoneurons, whereas the remaining 10% can be explained by serotonergic mechanisms that have net inhibitory effect on hypoglossal nerve activity during REM sleep-like state. We hypothesized that both noradrenergic and serotonergic state-dependent mechanisms indirectly control hypoglossal motoneuron excitability during REM sleep; their activities are integrated and mediated to hypoglossal motoneurons by reticular formation neurons. In addition, we proposed a brainstem neural circuit that can explain the new findings.

• Publication year

  2015

• Venue

  Frontiers in Neurology

• Publication date

  2015-12-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fneur.2015.00254PMID 26648908PMCID 4664632
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Upper Airway Stimulation for Obstructive Sleep Apnea: Past, Present, and Future.

  2015cited by this paper
• Postsynaptic inhibition of hypoglossal motoneurons produces atonia of the genioglossal muscle during rapid eye movement sleep.

  2015cited by this paper
• A growing problem

  2014cited by this paper
• Control of hypoglossal motoneurones during naturally occurring sleep and wakefulness in the intact, unanaesthetized cat: a field potential study

  2014cited by this paper
• HIGHLIGHTED TOPIC Upper Airway Control and Function: Implications for Sleep-Disordered Breathing Electrical stimulation of the hypoglossal nerve: a potential therapy

  2014cited by this paper
• New Therapies for Obstructive Sleep Apnea

  2014cited by this paper
• Noradrenergic modulation of masseter muscle activity during natural rapid eye movement sleep requires glutamatergic signalling at the trigeminal motor nucleus

  2014cited by this paper
• Drug therapy for obstructive sleep apnoea in adults.

  2013cited by this paper
• Identification of the mechanism mediating genioglossus muscle suppression in REM sleep.

  2013cited by this paper
• Control of sleep and wakefulness.

  2012cited by this paper
• Identification of the Transmitter and Receptor Mechanisms Responsible for REM Sleep Paralysis

  2012cited by this paper
• Obstructive sleep apnea: a growing problem.

  2009cited by this paper
• Differential localization of carbachol‐ and bicuculline‐sensitive pontine sites for eliciting REM sleep‐like effects in anesthetized rats

  2009cited by this paper
• The influence of obstructive sleep apnea and gender on genioglossus activity during rapid eye movement sleep.

  2009cited by this paper
• Unraveling the mechanisms of REM sleep atonia.

  2008cited by this paper
• NHIBITION OF PONTINE NORADRENERGIC A7 CELLS REDUCES

  2008cited by this paper
• Obstructive sleep apnea in older adults.

  2008cited by this paper
• An Endogenous Glutamatergic Drive onto Somatic Motoneurons Contributes to the Stereotypical Pattern of Muscle Tone across the Sleep–Wake Cycle

  2008cited by this paper
• Fos expression in pontomedullary catecholaminergic cells following rapid eye movement sleep-like episodes elicited by pontine carbachol in urethane-anesthetized rats.

  2008cited by this paper
• Inhibition of pontine noradrenergic A7 cells reduces hypoglossal nerve activity in rats.

  2008cited by this paper
• The motor atonia of REM sleep: a critical topics forum. Introduction.

  2008cited by this paper
• A neurotoxinological approach to the treatment of obstructive sleep apnoea.

  2007cited by this paper
• Obstructive Sleep Apnea and its Relationship to Cardiac Arrhythmias

  2007cited by this paper
• Genioglossus premotoneurons and the negative pressure reflex in rats

  2007cited by this paper
• Current trends in the treatment of obstructive sleep apnea.

  2007cited by this paper
• Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease.

  2007influential reference
• Pathophysiologic mechanisms in REM sleep behavior disorder

  2007cited by this paper
• Drug therapy for obstructive sleep apnoea in adults.

  2006cited by this paper
• Endogenous excitatory drive modulating respiratory muscle activity across sleep-wake states.

  2006cited by this paper
• Respiratory activation of the genioglossus muscle involves both non-NMDA and NMDA glutamate receptors at the hypoglossal motor nucleus in vivo.

  2006cited by this paper
• Noradrenergic, serotonergic and GABAergic antagonists injected together into the XII nucleus abolish the REM sleep‐like depression of hypoglossal motoneuronal activity

  2005influential reference
• Past, present--and future?

  2005cited by this paper
• Pathogenesis of obstructive and central sleep apnea.

  2005cited by this paper
• REM sleep-like atonia of hypoglossal (XII) motoneurons is caused by loss of noradrenergic and serotonergic inputs.

  2005influential reference
• Obstructive sleep apnea as a risk factor for stroke and death.

  2005cited by this paper
• Neurobehavioral Functioning in Obstructive Sleep Apnea: Differential Effects of Sleep Quality, Hypoxemia and Subjective Sleepiness

  2004cited by this paper
• Combined antagonism of aminergic excitatory and amino acid inhibitory receptors in the XII nucleus abolishes REM sleep-like depression of hypoglossal motoneuronal activity.

  2004cited by this paper
• Performance vigilance task and sleepiness in patients with sleep-disordered breathing

  2004cited by this paper
• Quality of life in bed partners of patients with obstructive sleep apnea or hypopnea after treatment with continuous positive airway pressure.

  2003cited by this paper
• Cognitive dysfunction in patients with obstructive sleep apnea (OSA): partial reversibility after continuous positive airway pressure (CPAP).

  2003cited by this paper
• Obstructive sleep apnea: implications for cardiac and vascular disease.

  2003cited by this paper
• Pharmacological characterization of serotonergic receptor activity in the hypoglossal nucleus.

  2003cited by this paper
• Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: An In Vivo Microdialysis Study

  2003cited by this paper
• Role of inhibitory amino acids in control of hypoglossal motor outflow to genioglossus muscle in naturally sleeping rats

  2003cited by this paper
• Cardiovascular consequences of obstructive sleep apnea.

  2003cited by this paper
• The rat ponto‐medullary network responsible for paradoxical sleep onset and maintenance: a combined microinjection and functional neuroanatomical study

  2002cited by this paper
• REM sleep behavior disorder: clinical, developmental, and neuroscience perspectives 16 years after its formal identification in SLEEP.

  2002cited by this paper
• A5 cells are silenced when REM sleep-like signs are elicited by pontine carbachol.

  2002cited by this paper
• Carbachol models of REM sleep: recent developments and new directions.

  2001cited by this paper
• Association of Sleep-Disordered Breathing, Sleep Apnea, and Hypertension in a Large Community-Based Study

  2000cited by this paper
• Relations among hypoxemia, sleep stage, and bradyarrhythmia during obstructive sleep apnea.

  2000cited by this paper
• Functional anatomy of the hypoglossal innervated muscles of the rat tongue: A model for elongation and protrusion of the mammalian tongue

  2000cited by this paper
• Methysergide delays the decompensatory responses to severe hemorrhage by activating 5-HT(1A) receptors.

  2000cited by this paper
• Changes in electrophysiological properties of cat hypoglossal motoneurons during carbachol-induced motor inhibition.

  2000cited by this paper
• Activation of Pontine and Medullary Motor Inhibitory Regions Reduces Discharge in Neurons Located in the Locus Coeruleus and the Anatomical Equivalent of the Midbrain Locomotor Region

  2000cited by this paper
• Association of sleep-disordered breathing, sleep apnea, and hypertension in a large community-based study. Sleep Heart Health Study.

  2000cited by this paper
• Hypoglossal motoneurons are postsynaptically inhibited during carbachol-induced rapid eye movement sleep.

  1999cited by this paper
• Population-based study of sleep-disordered breathing as a risk factor for hypertension.

  1997cited by this paper
• Differential sensitivity of laryngeal and pharyngeal motoneurons to iontophoretic application of serotonin.

  1997cited by this paper
• Behaviour of raphe cells projecting to the dorsomedial medulla during carbachol‐induced atonia in the cat.

  1996cited by this paper
• State-dependent phenomena in cat masseter motoneurons.

  1996cited by this paper
• Presynaptic depression of excitatory synaptic inputs to rat hypoglossal motoneurons by muscarinic M2 receptors.

  1996cited by this paper
• The control of jaw-opener motoneurons during active sleep.

  1994cited by this paper
• Sleep patterning and behaviour in cats with pontine lesions creating REM without atonia

  1994cited by this paper
• Influence of sleep on genioglossus muscle activation by negative pressure in normal men.

  1993cited by this paper
• Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition.

  1993cited by this paper
• Symposium: Normal and abnormal REM sleep regulation: REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature.

  1993cited by this paper
• REM sleep behaviour disorder: an update on a series of 96 patients and a review of the world literature

  1993cited by this paper
• Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism).

  1992cited by this paper
• Factors impairing daytime performance in patients with sleep apnea/hypopnea syndrome.

  1992cited by this paper
• Polysomnographic features of REM sleep behavior disorder

  1992cited by this paper
• PGO-related potentials in lumbar motoneurons during active sleep.

  1992cited by this paper
• The postsynaptic inhibitory control of lumbar motoneurons during the atonia of active sleep: effect of strychnine on motoneuron properties

  1991cited by this paper
• Suppression of the PGO-related lumbar motoneuron IPSP by strychnine.

  1990cited by this paper
• Effect of hypercapnia and hypoxia on respiratory muscle activation in humans.

  1989cited by this paper
• Evidence that glycine mediates the postsynaptic potentials that inhibit lumbar motoneurons during the atonia of active sleep

  1989cited by this paper
• Motoneuron properties during motor inhibition produced by microinjection of carbachol into the pontine reticular formation of the decerebrate cat.

  1987cited by this paper
• Activity of serotonin-containing neurons in the nucleus raphe pallidus of freely moving cats.

  1982cited by this paper
• Raphe unit activity in freely moving cats: correlation with level of behavioral arousal.

  1979cited by this paper
• Intracellular analysis of trigeminal motoneuron activity during sleep in the cat.

  1978cited by this paper
• Recent Developments and New Directions

  1974cited by this paper
• Corresponding Author and Requests for Reprints:

  year unknowncited by this paper

• Characterisation of sleep apneas and respiratory circuitry in mice lacking CDKL5

  2024cites this paper
• Chronic Intermittent Hypoxia Attenuates Noradrenergic Innervation of Hypoglossal Motor Nucleus.

  2023cites this paper
• Activity of pontine A7 noradrenergic neurons is suppressed during REM sleep

  2022cites this paper
• Impact of cold and flu medication on obstructive sleep apnoea and its underlying traits: A pilot randomized controlled trial

  2021cites this paper
• The α3 and α4 nicotinic acetylcholine receptor (nAChR) subunits in the brainstem medulla of sudden infant death syndrome (SIDS).

  2019cites this paper
• Muscarinic Inhibition of Hypoglossal Motoneurons: Possible Implications for Upper Airway Muscle Hypotonia during REM Sleep

  2019cites this paper
• Exposure to 835 MHz radiofrequency electromagnetic field induces autophagy in hippocampus but not in brain stem of mice

  2018cites this paper
• Contribution of Neurochemical Inputs to the Decrease of Motoneuron Excitability During Non-REM and REM Sleep: A Systematic Review

  2018cites this paper
• Neuroanatomical Basis of State-Dependent Activity of Upper Airway Muscles

  2018cites this paper
• Respiratory Physiology & Neurobiology airway muscle tone but participate in NREM sleep-related depression of these muscles

  2017influential citation
• Computational model of brainstem circuit for state-dependent control of hypoglossal motoneurons

  2017influential citation
• Catecholaminergic A1/C1 neurons contribute to the maintenance of upper airway muscle tone but may not participate in NREM sleep-related depression of these muscles.

  2017influential citation
• Activation of autophagy at cerebral cortex and apoptosis at brainstem are differential responses to 835 MHz RF-EMF exposure

  2017cites this paper
• Noradrenergic Activation of Hypoglossal Nucleus Modulates the Central Regulation of Genioglossus in Chronic Intermittent Hypoxic Rats

  2017cites this paper
• Intermittent hypercapnic hypoxia effects on the nicotinic acetylcholine receptors in the developing piglet hippocampus and brainstem

  2017cites this paper
• Neural Control of the Upper Airway: Respiratory and State-Dependent Mechanisms.

  2016cites this paper
• Respiratory Physiology & Neurobiology

  year unknowninfluential citation