Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition

Kubin, Leszek; Kimura, Hiroshi; Tojima, Hirokazu; Davies, Richard O.; Pack, Allan I.

doi:10.1016/0006-8993(93)90517-q

Cited by 107 publications

(86 citation statements)

References 34 publications

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“…This conclusion is congruent with the findings that suppression of respiratory-related genioglossus muscle activity during either natural or carbachol-induced REM sleep could not be reversed by antagonism of glycinergic or GABA A -mediated inhibition at the hypoglossal motonucleus in rats (Kubin et al, 1993;Morrison et al, 2003). We conclude that glycinergic and GABA Amediated inhibition of motoneurons is not the mechanism mediating the loss of postural muscle tone during REM sleep.…”

Section: A Phasic Inhibitory Drive Functions To Oppose Muscle Twitchesupporting

confidence: 89%

“…Studies of respiratory motor control in sleep, however, have shown that neither glycinergic nor GABA A -mediated inhibition at the hypoglossal motor pool mediates the typical suppression of inspiratory genioglossus muscle activity during natural or carbachol-induced REM sleep (Kubin et al, 1993;Morrison et al, 2003). Although inspiratory muscle suppression in REM sleep is not caused by glycinergic/GABAergic inhibition of respiratory motoneurons, it has never been determined whether the REMspecific IPSPs recorded from nonrespiratory motoneurons (e.g., trigeminal) are in fact responsible for triggering REM atonia in postural muscles.…”

Section: Introductionmentioning

confidence: 99%

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Glycinergic and GABA_A-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Brooks¹,

Peever²

2008

J. Neurosci.

117

106

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A hallmark of rapid eye movement (REM) sleep is a potent suppression of postural muscle tone. Motor control in REM sleep is unique because it is characterized by flurries of intermittent muscle twitches that punctuate muscle atonia. Because somatic motoneurons are bombarded by strychnine-sensitive IPSPs during REM sleep, it is assumed that glycinergic inhibition underlies REM atonia. However, it has never been determined whether glycinergic inhibition of motoneurons is indeed responsible for triggering the loss of postural muscle tone during REM sleep. Therefore, we used reverse microdialysis, electrophysiology, and pharmacological and histological methods to determine whether glycinergic and/or GABA A -mediated neurotransmission at the trigeminal motor pool mediates masseter muscle atonia during REM sleep in rats. By antagonizing glycine and GABA A receptors on trigeminal motoneurons, we unmasked a tonic glycinergic/GABAergic drive at the trigeminal motor pool during waking and non-rapid eye movement (NREM) sleep. Blockade of this drive potently increased masseter muscle tone during both waking and NREM sleep. This glycinergic/GABAergic drive was immediately switched-off and converted into a phasic glycinergic drive during REM sleep. Blockade of this phasic drive potently provoked muscle twitch activity in REM sleep; however, it did not prevent or reverse REM atonia. Muscle atonia in REM even persisted when glycine and GABA A receptors were simultaneously antagonized and trigeminal motoneurons were directly activated by glutamatergic excitation, indicating that a powerful, yet unidentified, inhibitory mechanism overrides motoneuron excitation during REM sleep. Our data refute the prevailing hypothesis that REM atonia is caused by glycinergic inhibition. The inhibitory mechanism mediating REM atonia therefore requires reevaluation.

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Section: A Phasic Inhibitory Drive Functions To Oppose Muscle Twitchesupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Glycinergic and GABA_A-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Brooks¹,

Peever²

2008

J. Neurosci.

117

106

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“…An increase in glycine release but no significant change in GABA release in the ventral horn was seen with electrical stimulationinduced atonia. Although Kubin et al (1993) hypothesized that glycine and GABA did not have the same role in the XII nucleus as it did in the trigeminal motor nucleus and ventral horn during pontine carbachol-induced atonia, we observed a significant increase in glycine and GABA release of the XII nucleus of the same magnitude as seen in the ventral horn during PIA stimulationinduced atonia. Our results suggest that glycine and GABA have a similar role in the regulation of hypoglossal and spinal motoneu- ron activity during PIA stimulation-induced muscle tone suppression.…”

Section: Discussioncontrasting

confidence: 76%

“…Thus, they concluded that glycine plays a critical role in the control of REM sleep atonia in the postural and upper airway muscles. In contrast, Kubin et al (1993) hypothesized that inhibitory amino acids might not be important in the regulation of hypoglossal motoneuron activity during REM sleep and that pontine inhibition of respiratory motoneurons was attributable to disfacilitation via cessation of serotonin release rather than glycinergic inhibition.…”

Section: Introductionmentioning

confidence: 99%

Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: AnIn VivoMicrodialysis Study

2003

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We hypothesized that cessation of brainstem monoaminergic systems and an activation of brainstem inhibitory systems are both involved in pontine inhibitory area (PIA) stimulation-induced muscle atonia. In our previous study (Lai et al., 2001), we found a decrease in norepinephrine and serotonin release in motoneuron pools during PIA stimulation-induced muscle tone suppression. We now demonstrate an increase in inhibitory amino acid release in motor nuclei during PIA stimulation in the decerebrate cat using in vivo microdialysis and HPLC analysis techniques. Microinjection of acetylcholine into the PIA elicited muscle atonia and simultaneously produced a significant increase in both glycine and GABA release in both the hypoglossal nucleus and the lumbar ventral horn. Glycine release increased by 74% in the hypoglossal nucleus and 50% in the spinal cord. GABA release increased by 31% in the hypoglossal nucleus and 64% in the spinal cord during atonia induced by cholinergic stimulation of the PIA. As with cholinergic stimulation, 300 msec train electrical stimulation of the PIA elicited a significant increase in glycine release in the hypoglossal nucleus and ventral horn. GABA release was significantly increased in the hypoglossal nucleus but not in the spinal cord during electrical stimulation of the PIA. Glutamate release in the motor nuclei was not significantly altered during atonia induced by electrical or acetylcholine stimulation of the PIA. We suggest that both glycine and GABA play important roles in the regulation of upper airway and postural muscle tone. A combination of decreased monoamine and increased inhibitory amino acid release in motoneuron pools causes PIA-induced atonia and may be involved in atonia linked to rapid eye-movement sleep.

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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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Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition

Cited by 107 publications

References 34 publications

Glycinergic and GABA_A-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Glycinergic and GABA_A-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: AnIn VivoMicrodialysis Study

Synaptic Control of Motoneuronal Excitability

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Suppression of hypoglossal motoneurons during the carbachol-induced atonia of REM sleep is not caused by fast synaptic inhibition

Cited by 107 publications

References 34 publications

Glycinergic and GABAA-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Glycinergic and GABAA-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Changes in Inhibitory Amino Acid Release Linked to Pontine-Induced Atonia: AnIn VivoMicrodialysis Study

Synaptic Control of Motoneuronal Excitability

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Product

Resources

About

Glycinergic and GABA_A-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia

Glycinergic and GABA_A-Mediated Inhibition of Somatic Motoneurons Does Not Mediate Rapid Eye Movement Sleep Motor Atonia