Interaction of Serotonergic Excitatory Drive to Hypoglossal Motoneurons With Carbachol-Induced, REM Sleep-Like Atonia

Kubin, Leszek; Tojima, Hirokazu; Reignier, Clotilde; Davies, Richard O.

doi:10.1093/sleep/19.3.187

Cited by 68 publications

(44 citation statements)

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“…On the basis of those findings, attempts were made to determine whether any one mechanism can explain the REM sleep-related depression of activity in hypoglossal (XII) motoneurons, the source of motor innervation of the genioglossus, a major upper airway dilator. However, infusion of 5-HT into the XII nucleus only partially blunted the REM sleep-like suppression of XII nerve activity elicited in decerebrate cats by pontine carbachol injections (10), and perfusion of the XII nucleus with 5-HT in chronically instrumented rats did not prevent the depression of genioglossal activity during REM sleep (11). Microinjections into the XII nucleus of either strychnine, a glycinergic receptor antagonist, or bicuculline, a GABA A receptor antagonist, had little effect on the suppression of XII nerve activity elicited by pontine carbachol in decerebrate cats (12); a similar observation was made in chronically instrumented, naturally sleeping rats (13).…”

mentioning

confidence: 83%

REM Sleep–like Atonia of Hypoglossal (XII) Motoneurons Is Caused by Loss of Noradrenergic and Serotonergic Inputs

Fenik

Davies²,

Kubin

2005

Am J Respir Crit Care Med

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171

248

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Rationale-Studies of hypoglossal (XII) motoneurons that innervate the genioglossus muscle, an upper airway dilator, suggested that the suppression of upper airway motor tone during REM sleep is caused by withdrawal of excitation mediated by norepinephrine and serotonin.Objectives-Our objectives were to determine whether antagonism of aminergic receptors located in the XII nucleus region can abolish the REM sleep-like atonia of XII motoneurons, and whether both serotonergic and noradrenergic antagonists are required to achieve this effect.Methods-REM sleep-like episodes were elicited in anesthetized rats by pontine carbachol injections before and at various times after microinjection of prazosin and methysergide combined, or of only one of the drugs, into the XII nucleus. Measurements and MainResults-Spontaneous XII nerve activity was significantly reduced, by 35 to 81%, by each antagonist alone and in combination, indicating that XII motoneurons were under both noradrenergic and serotonergic endogenous excitatory drives. During the 32 to 81 min after microinjections of both antagonists, pontine carbachol caused no depression of XII nerve activity, whereas other characteristic effects (activation of the hippocampal and cortical EEG, and slowing of the respiratory rate) remained intact. A partial recovery of the depressant effect of carbachol then occurred parallel to the recovery of spontaneous XII nerve activity from the depressant effect of the antagonists. Microinjections of either antagonist alone did not eliminate the depressant effect of carbachol.Conclusions-The REM sleep-like depression of XII motoneuronal activity induced by pontine carbachol can be fully accounted for by the combined withdrawal of noradrenergic and serotonergic effects on XII motoneurons.

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mentioning

confidence: 83%

REM Sleep–like Atonia of Hypoglossal (XII) Motoneurons Is Caused by Loss of Noradrenergic and Serotonergic Inputs

Fenik

Davies²,

Kubin

2005

Am J Respir Crit Care Med

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171

248

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“…It is possible that whether the response of hypoglossal neurons to NE application is excitation or depression may depend on the dosage, as shown previously (Armstrong-James and Fox, 1983), or the animal species used. Indeed, it has been reported that NE is more effective than 5-HT in increasing GG muscle activity in rats (Fenik et al, 2005b), whereas 5-HT is highly effective in both dogs and cats (Kubin et al, 1992(Kubin et al, , 1996Veasey et al, 1996). Moreover, in rats in vivo, antagonism of alpha-1 adrenergic receptors in the hypoglossal nucleus region has clear excitatory effects on GG muscle activity (Chan et al, 2006;Fenik et al, 2005b).…”

Section: Ne and Gg Muscle Activitymentioning

confidence: 99%

“…Because the hypotonia of upper airway muscle tone occurs in parallel with a decrease in postural muscle activity, it has been postulated that the suppression of GG muscle activity during PS might be due to an inhibitory mechanism (Yamuy et al, 1999). However, microinjections into the HMN of either strychnine, a glycinergic receptor antagonist, or bicuculline, a GABA A receptor antagonist, have little effect in PS-like atonia in cats (Kubin et al, 1993(Kubin et al, , 1996 or in naturally sleeping rats (Morrison et al, 2003), suggesting that the suppression of GG muscle activity during PS may not be primarily caused by an inhibitory mechanism. In addition, antagonism of glycine and GABA A receptors on trigeminal motoneurons does not prevent or reverse PS atonia (Brooks and Peever, 2008).…”

Section: Introductionmentioning

confidence: 99%

“…The HMN receives dense serotonergic inputs (Kubin et al, 1996;Li et al, 1993;Manaker and Tischler, 1993), and 5-hydroxytryptamine (serotonin, 5-HT) increases the excitability of HMN in vitro (Berger et al, 1992). When applied to the HMN in vivo, 5-HT attenuates the decrease in XII nerve or GG muscle activity seen in carbachol-induced PS-like atonia in decerebrate cats (Kubin et al, 1993) or in naturally sleeping rats (Jelev et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Application of histamine or serotonin to the hypoglossal nucleus increases genioglossus muscle activity across the wake–sleep cycle

Neuzeret

Sakai

Gormand

et al. 2009

Journal of Sleep Research

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SUMMAR Y The decrease in genioglossus (GG) muscle activity during sleep, especially rapid eye movement (REM) or paradoxical sleep, can lead to airway occlusion and obstructive sleep apnoea (OSA). The hypoglossal nucleus innervating the GG muscle is under the control of serotonergic, noradrenergic and histaminergic neurons that cease firing during paradoxical sleep. The objectives of this study were to determine the effect on GG muscle activity during different wake-sleep states of the microdialysis application of serotonin, histamine (HA) or noradrenaline (NE) to the hypoglossal nucleus in freely moving cats. Six adult cats were implanted with electroencephalogram, electrooculogram and neck electromyogram electrodes to record wake-sleep states and with GG muscle and diaphragm electrodes to record respiratory muscle activity. Microdialysis probes were inserted into the hypoglossal nucleus for monoamine application. Changes in GG muscle activity were assessed by power spectrum analysis. In the baseline conditions, tonic GG muscle activity decreased progressively and significantly from wakefulness to slow-wave sleep and even further during slow-wave sleep with ponto-geniculo-occipital waves and paradoxical sleep. Application of serotonin or HA significantly increased GG muscle activity during the wake-sleep states when compared with controls. By contrast, NE had no excitatory effect. Our results indicate that both serotonin and HA have a potent excitatory action on GG muscle activity, suggesting multiple aminergic control of upper airway muscle activity during the wake-sleep cycle. These data might help in the development of pharmacological approaches for the treatment of OSA.k e y w o r d s genioglossus, histamine, hypoglossus, noradrenaline, obstructive sleep apnoea, serotonin, sleep INTRODUCTIONThe activity of the genioglossus (GG) muscle, innervated by the hypoglossal (XII) motor nucleus (HMN), contributes to the maintenance of upper airway patency (Ryan and Bradley, 2005;White, 2006). During sleep, especially rapid eye movement (REM) or paradoxical sleep (PS), GG muscle activity decreases in animals (Horner et al., 2002;Megirian et al., 1985) and humans (Katz and White, 2004;Sauerland and Harper, 1976). In individuals with an anatomically small pharyngeal airway, this decrease in GG muscle activity can lead to airway occlusion (Remmers et al., 1978), i.e. obstructive sleep apnoea (OSA), a sleep disorder affecting up to 4% of adults (Young et al., 1993). The mechanisms responsible for this selective obstruction of the upper airway during PS remain unclear and pharmacological therapies have not Correspondence: Pierre-Charles Neuzeret, INSERM U628, Physiologie Inte´gre´e du Syste`me dÕEveil,

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“…Among cranial motoneurons, the mechanism of inhibition varies during REM sleep. For example, in trigeminal motoneurons (649-651, 965, 1029), inhibition is glycinergic, whereas the inhibition of hypoglossal motoneuron activity results primarily from disfacilitation (669,670,672,1378). The mechanisms underlying this differential control are incompletely understood but remain of considerable interest because of their potential involvement in conditions such as cataplexy, REM behavior disorder, and state-dependent respiratory disorders such as obstructive sleep apnea and perhaps sudden infant death syndrome.…”

Section: C) Presynaptic Actions Of Gaba a Receptorsmentioning

confidence: 99%

Synaptic Control of Motoneuronal Excitability

Rekling

Funk

Bayliss

et al. 2000

Physiological Reviews

531

482

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Movement, the fundamental component of behavior and the principal extrinsic action of the brain, is produced when skeletal muscles contract and relax in response to patterns of action potentials generated by motoneurons. The processes that determine the firing behavior of motoneurons are therefore important in understanding the transformation of neural activity to motor behavior. Here, we review recent studies on the control of motoneuronal excitability, focusing on synaptic and cellular properties. We first present a background description of motoneurons: their development, anatomical organization, and membrane properties, both passive and active. We then describe the general anatomical organization of synaptic input to motoneurons, followed by a description of the major transmitter systems that affect motoneuronal excitability, including ligands, receptor distribution, pre-and postsynaptic actions, signal transduction, and functional role. Glutamate is the main excitatory, and GABA and glycine are the main inhibitory transmitters acting through ionotropic receptors. These amino acids signal the principal motor commands from peripheral, spinal, and supraspinal structures. Amines, such as serotonin and norepinephrine, and neuropeptides, as well as the glutamate and GABA acting at metabotropic receptors, modulate motoneuronal excitability through pre-and postsynaptic actions. Acting principally via second messenger systems, their actions converge on common effectors, e.g., leak K + current, cationic inward current, hyperpolarization-activated inward current, Ca 2+ channels, or presynaptic release processes. Together, these numerous inputs mediate and modify incoming motor commands, ultimately generating the coordinated firing patterns that underlie muscle contractions during motor behavior.

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Interaction of Serotonergic Excitatory Drive to Hypoglossal Motoneurons With Carbachol-Induced, REM Sleep-Like Atonia

Cited by 68 publications

References 0 publications

REM Sleep–like Atonia of Hypoglossal (XII) Motoneurons Is Caused by Loss of Noradrenergic and Serotonergic Inputs

REM Sleep–like Atonia of Hypoglossal (XII) Motoneurons Is Caused by Loss of Noradrenergic and Serotonergic Inputs

Application of histamine or serotonin to the hypoglossal nucleus increases genioglossus muscle activity across the wake–sleep cycle

Synaptic Control of Motoneuronal Excitability

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