scholarly journals Pre- and postsynaptic modulations of hypoglossal motoneurons by α-adrenoceptor activation in wild-type and Mecp2−/Y mice

2013 ◽  
Vol 305 (10) ◽  
pp. C1080-C1090 ◽  
Author(s):  
Xiao-Tao Jin ◽  
Ningren Cui ◽  
Weiwei Zhong ◽  
Xin Jin ◽  
Zhongying Wu ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Upper Airway ◽  
Membrane Properties ◽  
Compensatory Mechanism ◽  
Tongue Movement ◽  
Wild Type ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Therapeutical Modalities ◽  
Intrinsic Membrane Properties

Hypoglossal motoneurons (HNs) control tongue movement and play a role in maintenance of upper airway patency. Defects in these neurons may contribute to the development of sleep apnea and other cranial motor disorders including Rett syndrome (RTT). HNs are modulated by norepinephrine (NE) through α-adrenoceptors. Although postsynaptic mechanisms are known to play a role in this effect, how NE modulates the synaptic transmissions of HNs remains poorly understood. More importantly, the NE system is defective in RTT, while how the defect affects HNs is unknown. Believing that information of NE modulation of HNs may help the understanding of RTT and the design of new therapeutical interventions to motor defects in the disease, we performed these studies in which glycinergic inhibitory postsynaptic currents and intrinsic membrane properties were examined in wild-type and Mecp2 −/Y mice, a mouse of model of RTT. We found that activation of α1-adrenoceptor facilitated glycinergic synaptic transmission and excited HNs. These effects were mediated by both pre- and postsynaptic mechanisms. The latter effect involved an inhibition of barium-sensitive G protein-dependent K+ currents. The pre- and postsynaptic modulations of the HNs by α1-adrenoceptors were not only retained in Mecp2-null mice but also markedly enhanced, which appears to be a compensatory mechanism for the deficiencies in NE and GABAergic synaptic transmission. The existence of the endogenous compensatory mechanism is an encouraging finding, as it may allow therapeutical modalities to alleviate motoneuronal defects in RTT.

Inspiratory coactivation of the genioglossus enlarges retroglossal space in laryngectomized humans

1996 ◽  
Vol 80 (5) ◽  
pp. 1595-1604 ◽  
Author(s):  
I. Kobayashi ◽  
A. Perry ◽  
J. Rhymer ◽  
B. Wuyam ◽  
P. Hughes ◽  
...  
Keyword(s):  
Upper Airway ◽  
Dependent Manner ◽  
Tongue Movement ◽  
Forward Movement ◽  
Upper Airways ◽  
Posterior Aspect ◽  
Airway Patency ◽  
Significant Movement ◽  
Tongue Position ◽  
Tracheal Stoma

To investigate the relationship between the electrical activity of the genioglossus (GG-EMG) and associated tongue movement, seven laryngectomized subjects breathing through a tracheal stoma (without pressure or flow change in the upper airway) were studied in the supine position. Tongue movement, with the use of lateral fluoroscopy, and GG-EMG expressed as a percentage of maximum voluntary genioglossal activation were monitored simultaneously during 1) spontaneous inspiration (SI), 2) resistive loaded inspiration (LI), and 3) rapid inspiration (RI). Tongue position during each maneuver was compared with its position during spontaneous expiration. Peak GG-EMG during the three maneuvers was significantly different from each other (SI: 5.4 +/- 1.6, LI: 11.9 +/- 1.8, and RI: 51.6 +/- 9.4 (SE) %, respectively). Associated forward movement of the posterior aspect of the tongue was minimum during SI; however, significant movement was observed during LI, and this was increased during RI. Significant covariance existed between peak GG-EMG and this movement. Genioglossal coactivation with inspiration enlarges the glossopharyngeal airway, particularly in its caudal part. In subjects with intact upper airways, this activation may protect or enhance upper airway patency in an effort-dependent manner.

Arterial chemoreceptor input to respiratory hypoglossal motoneurons

1990 ◽  
Vol 69 (2) ◽  
pp. 700-709 ◽  
Author(s):  
S. W. Mifflin
Keyword(s):  
Membrane Potential ◽  
Upper Airway ◽  
Excitatory Input ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
End Tidal ◽  
Carotid Body Chemoreceptors ◽  
Excitatory Drive ◽  
Arterial Chemoreceptor

To better understand the role of the arterial chemoreceptors in the regulation of upper airway patency at the level of the oropharynx, intracellular recordings were obtained from inspiratory hypoglossal motoneurons (IHMs), and the responses to selective activation of the carotid body chemoreceptors were examined. In pentobarbital-anesthetized, vagotomized, paralyzed, and artificially ventilated cats, chemoreceptor activation enhanced the inspiratory depolarization of membrane potential in 32 of 36 IHMs. This was manifested as an increase in either the amplitude (n = 13) or duration (n = 3) or an increase in both amplitude and duration (n = 16) of the inspiratory membrane potential depolarization. The amplitude and duration of the inspiratory membrane potential depolarization increased 98 +/- 15% (n = 29) and 78 +/- 13% (n = 19), respectively. Similar patterns of enhanced activity (increased duration and/or amplitude of membrane depolarization) were observed in five expiratory hypoglossal motoneurons (EHMs) after chemoreceptor activation. In 16 of the 32 IHMs, chemoreceptor activation also evoked changes in IHM membrane potential during expiration: enhanced post-inspiratory discharge (n = 6), expiratory depolarization/discharge (n = 6), and tonic depolarization/discharge, which persisted for several respiratory cycles (n = 4). The arterial chemoreceptors provide a powerful excitatory input to IHMs during both inspiration and expiration. This excitatory drive to IHMs and EHMs will aid in the maintenance of upper airway patency throughout the respiratory cycle during increases in end-tidal CO2.

scholarly journals Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons

1997 ◽  
Vol 83 (6) ◽  
pp. 1890-1899 ◽  
Author(s):  
Steven W. Mifflin
Keyword(s):  
Frequency Dependence ◽  
Stimulus Frequency ◽  
Superior Laryngeal Nerve ◽  
Upper Airway ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Afferent Fibers ◽  
Complex Motor ◽  
Afferent Inputs ◽  
Motor Acts

Mifflin, Steven W. Intensity and frequency dependence of laryngeal afferent inputs to respiratory hypoglossal motoneurons. J. Appl. Physiol. 83(6): 1890–1899, 1997.—Inspiratory hypoglossal motoneurons (IHMs) mediate contraction of the genioglossus muscle and contribute to the regulation of upper airway patency. Intracellular recordings were obtained from antidromically identified IHMs in anesthetized, vagotomized cats, and IHM responses to electrical activation of superior laryngeal nerve (SLN) afferent fibers at various frequencies and intensities were examined. SLN stimulus frequencies <2 Hz evoked an excitatory-inhibitory postsynaptic potential (EPSP-IPSP) sequence or only an IPSP in most IHMs that did not change in amplitude as the stimulus was maintained. During sustained stimulus frequencies of 5–10 Hz, there was a reduction in the amplitude of SLN-evoked IPSPs with time with variable changes in the EPSP. At stimulus frequencies >25 Hz, the amplitude of EPSPs and IPSPs was reduced over time. At a given stimulus frequency, increasing stimulus intensity enhanced the decay of the SLN-evoked postsynaptic potentials (PSPs). Frequency-dependent attenuation of SLN inputs to IHMs also occurred in newborn kittens. These results suggest that activation of SLN afferents evokes different PSP responses in IHMs depending on the stimulus frequency. At intermediate frequencies, inhibitory inputs are selectively filtered so that excitatory inputs predominate. At higher frequencies there was no discernible SLN-evoked PSP temporally locked to the SLN stimuli. Alterations in SLN-evoked PSPs could play a role in the coordination of genioglossal contraction during respiration, swallowing, and other complex motor acts where laryngeal afferents are activated.

scholarly journals Serotonergic Modulation of Inspiratory Hypoglossal Motoneurons in Decerebrate Dogs

2006 ◽  
Vol 95 (6) ◽  
pp. 3449-3459 ◽  
Author(s):  
Ivo F. Brandes ◽  
Edward J. Zuperku ◽  
Astrid G. Stucke ◽  
Danica Jakovcevic ◽  
Francis A. Hopp ◽  
...  
Keyword(s):  
Upper Airway ◽  
Discharge Pattern ◽  
Receptor Subtype ◽  
Drug Induced ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Single Neuron Recording ◽  
Induced Changes

Inspiratory hypoglossal motoneurons (IHMNs) maintain upper airway patency. However, this may be compromised during sleep and by sedatives, potent analgesics, and volatile anesthetics by either depression of excitatory or enhancement of inhibitory inputs. In vitro data suggest that serotonin (5-HT), through the 5-HT2A receptor subtype, plays a key role in controlling the excitability of IHMNs. We hypothesized that in vivo 5-HT modulates IHMNs activity through the 5-HT2A receptor subtype. To test this hypothesis, we used multibarrel micropipettes for extracellular single neuron recording and pressure picoejection of 5-HT or ketanserin, a selective 5-HT2A receptor subtype antagonist, onto single IHMNs in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs. Drug-induced changes in neuronal discharge frequency ( Fn) and neuronal discharge pattern were analyzed using cycle-triggered histograms. 5-HT increased the control peak Fn to 256% and the time-averaged Fn to 340%. 5-HT increased the gain of the discharge pattern by 61% and the offset by 34 Hz. Ketanserin reduced the control peak Fn by 68%, the time-averaged Fn by 80%, and the gain by 63%. These results confirm our hypothesis that in vivo 5-HT is a potent modulator of IHMN activity through the 5-HT2A receptor subtype. Application of exogenous 5-HT shows that this mechanism is not saturated during hypercapnic hyperoxia. The two different mechanisms, gain modulation and offset change, indicate that 5-HT affects the excitability as well as the excitation of IHMNs in vivo.

scholarly journals GABA and glycine neurons from the ventral medullary region inhibit hypoglossal motoneurons

SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Olga Dergacheva ◽  
Thomaz Fleury-Curado ◽  
Vsevolod Y Polotsky ◽  
Matthew Kay ◽  
Vivek Jain ◽  
...  
Keyword(s):  
Rem Sleep ◽  
Muscle Tone ◽  
Upper Airway ◽  
Emg Activity ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Obstructive Sleep ◽  
Tongue Muscles

Abstract Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive sleep-related losses of upper airway patency that occur most frequently during rapid eye movement (REM) sleep. Hypoglossal motoneurons play a key role in regulating upper airway muscle tone and patency during sleep. REM sleep activates GABA and glycine neurons in the ventral medulla (VM) to induce cortical desynchronization and skeletal muscle atonia during REM sleep; however, the role of this brain region in modulating hypoglossal motor activity is unknown. We combined optogenetic and chemogenetic approaches with in-vitro and in-vivo electrophysiology, respectfully, in GAD2-Cre mice of both sexes to test the hypothesis that VM GABA/glycine neurons control the activity of hypoglossal motoneurons and tongue muscles. Here, we show that there is a pathway originating from GABA/glycine neurons in the VM that monosynaptically inhibits brainstem hypoglossal motoneurons innervating both tongue protruder genioglossus (GMNs) and retractor (RMNs) muscles. Optogenetic activation of ChR2-expressing fibers induced a greater postsynaptic inhibition in RMNs than in GMNs. In-vivo chemogenetic activation of VM GABA/glycine neurons produced an inhibitory effect on tongue electromyographic (EMG) activity, decreasing both the amplitude and duration of inspiratory-related EMG bursts without any change in respiratory rate. These results indicate that activation of GABA/glycine neurons from the VM inhibits tongue muscles via a direct pathway to both GMNs and RMNs. This inhibition may play a role in REM sleep associated upper airway obstructions that occur in patients with OSA.

Behaviors of hypoglossal hyoid motoneurons in laryngeal and vestibular reflexes and in deglutition and emesis

1998 ◽  
Vol 274 (4) ◽  
pp. R950-R955 ◽  
Author(s):  
Toshiro Umezaki ◽  
Ken Nakazawa ◽  
Alan D. Miller
Keyword(s):  
Single Cells ◽  
Upper Airway ◽  
Reflex Response ◽  
Hypoglossal Nucleus ◽  
Airway Protection ◽  
Related Activity ◽  
Airway Patency ◽  
Hypoglossal Motoneurons ◽  
Muscle Nerve ◽  
To Receive

Reflex responses of hypoglossal motoneurons innervating the geniohyoid (GH) and thyrohyoid (TH) muscles from the superior laryngeal (SLN) and vestibular nerves and their behaviors during fictive swallowing and vomiting were examined by recording both the extracellular activities of 11 single cells in the hypoglossal nucleus and GH and TH muscle nerve activity in eight decerebrate, paralyzed, and artificially ventilated cats. The majority of TH motoneurons were either active and/or exhibited shortened antidromic latencies during early expiration. In contrast, GH motoneurons did not exhibit any respiratory-related activity. Electrical single-shock stimulation of the SLN never evoked an excitatory reflex response on GH or TH motoneurons but rather evoked inhibitory responses on the THs. Unlike other hypoglossal motoneurons, GH and TH motoneurons do not appear to receive vestibular inputs. However, they can exhibit robust activities during fictive swallowing and vomiting, particularly during expulsion. Thus these motoneurons may play an important role in airway protection during swallowing and vomiting but not in controlling upper airway patency regulated by vestibular afferents.

scholarly journals Defects in brainstem neurons associated with breathing and motor function in the Mecp2R168X/Y mouse model of Rett syndrome

2016 ◽  
Vol 311 (6) ◽  
pp. C895-C909 ◽  
Author(s):  
Christopher M. Johnson ◽  
Weiwei Zhong ◽  
Ningren Cui ◽  
Yang Wu ◽  
Hao Xing ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rett Syndrome ◽  
Motor Function ◽  
Neurodevelopmental Disorder ◽  
Motor Dysfunction ◽  
Membrane Properties ◽  
Wild Type ◽  
Lower Body Weight ◽  
Associated Functions ◽  
Intrinsic Membrane Properties

Rett Syndrome (RTT) is an X-linked neurodevelopmental disorder caused mostly by disruption of the MECP2 gene. Among several RTT-like mouse models, one of them is a strain of mice that carries an R168X point mutation in Mecp2 and resembles one of the most common RTT-causing mutations in humans. Although several behavioral defects have previously been found in the Mecp2R168X/Y mice, alterations in nerve cells remain unknown. Here we compare several behavioral and cellular outcomes between this Mecp2R168X/Y model and a widely used Mecp2Bird/Y mouse model. With lower body weight and shorter lifespan than their wild-type littermates, the Mecp2R168X/Y mice showed impairments of breathing and motor function. Thus we studied brainstem CO2-chemosensitive neurons and propriosensory cells that are associated with these two functions, respectively. Neurons in the locus coeruleus (LC) of both mutant strains showed defects in their intrinsic membrane properties, including changes in action potential morphology and excessive firing activity. Neurons in the mesencephalic trigeminal nucleus (Me5) of both strains displayed a higher firing response to depolarization than their wild-type littermates, likely attributable to a lower firing threshold. Because the increased excitability in LC and Me5 neurons tends to impact the excitation-inhibition balances in brainstem neuronal networks as well as their associated functions, it is likely that the defects in the intrinsic membrane properties of these brainstem neurons contribute to the breathing abnormalities and motor dysfunction. Furthermore, our results showing comparable phenotypical outcomes of Mecp2R168X/Y mice with Mecp2Bird/Y mice suggest that both strains are valid animal models for RTT research.

Serotonergic Control of Cerebellar Mossy Fiber Activity by Modulation of Signal Transfer by Rat Pontine Nuclei Neurons

2002 ◽  
Vol 88 (2) ◽  
pp. 549-564 ◽  
Author(s):  
Martin Möck ◽  
Cornelius Schwarz ◽  
Peter Thier
Keyword(s):  
Synaptic Transmission ◽  
Receptor Antagonist ◽  
Membrane Properties ◽  
Cerebral Peduncle ◽  
Pontine Nuclei ◽  
Pass Filter ◽  
Paired Pulse ◽  
Paired Pulse Facilitation ◽  
Synaptic Facilitation ◽  
Intrinsic Membrane Properties

Serotonergic modulation of precerebellar nuclei may be crucial for the function of the entire cerebellar system. To study the effects of serotonin (5-HT) on neurons located within the pontine nuclei (PN), the main source of cerebellar mossy fibers, we performed standard intracellular recordings from PN neurons in a slice preparation of the rat pontine brain stem. Application of 5 μM 5-HT significantly altered several intrinsic membrane properties of PN neurons. First, it depolarized the somatic membrane potential by 6.5 ± 3.5 mV and increased the apparent input resistance from 49.5 ± 14.6 to 62.7 ± 21.1 MΩ. Second, 5-HT altered the I-V relationship of PN neurons: it decreased the inward rectification in hyperpolarizing direction, but increased it when depolarizing currents were applied. Third, it decreased the rheobase from 0.32 ± 0.14 to 0.24 ± 0.14 nA without affecting the firing threshold. Finally, the amplitude of medium-duration afterhyperpolarizations was reduced from −14.9 ± 2.0 to −12.3 ± 2.4 mV. Together, these 5-HT effects on the intrinsic membrane properties result in an increase in excitability and instantaneous firing rate. In addition, application of 5 μM 5-HT also modulated postsynaptic potentials (PSPs) evoked by electric stimulations within the cerebral peduncle. The amplitude, maximal slope, and integral of these PSPs were reduced to 46.2 ± 23.4%, 45.7 ± 23.7%, and 61.4 ± 28.4% of the control value, respectively. In contrast, we found no change in the decay and voltage dependence of PSPs. To test modulatory effects on short-term synaptic facilitation, we applied pairs of electrical stimuli at intervals between 10 and 1,000 ms. 5-HT selectively enhanced the paired-pulse facilitation for interstimulus-intervals >20 ms. The alteration of paired-pulse facilitation points to a presynaptic site of action for 5-HT effects on synaptic transmission. Pharmacological experiments suggested that pre- and postsynaptic effects of 5-HT were mediated by two different kinds of 5-HT receptors: changes in intrinsic membrane properties were blocked by the 5-HT2 receptor antagonist cinanserin while the reduction of PSPs was prevented by the 5-HT1 receptor antagonist cyanopindolol. In conclusion, 5-HT increases the excitability of PN neurons but decreases the synaptic transmission on them. The selective enhancement of synaptic facilitation may, however, allow high-frequency inputs to effectively drive PN neurons, thus the PN may act as a high-pass filter during periods of 5-HT release.

scholarly journals Effect of Head Elevation on Passive Upper Airway Collapsibility in Normal Subjects during Propofol Anesthesia

2011 ◽  
Vol 115 (2) ◽  
pp. 273-281 ◽  
Author(s):  
Masato Kobayashi ◽  
Takao Ayuse ◽  
Yuko Hoshino ◽  
Shinji Kurata ◽  
Shunji Moromugi ◽  
...  
Keyword(s):  
Upper Airway ◽  
Normal Subjects ◽  
Target Concentration ◽  
Airway Patency ◽  
Head Elevation ◽  
Jaw Opening ◽  
Airway Collapsibility ◽  
Upper Airway Collapsibility ◽  
Head Flexion ◽  
Male Subjects

Background Head elevation can restore airway patency during anesthesia, although its effect may be offset by concomitant bite opening or accidental neck flexion. The aim of this study is to examine the effect of head elevation on the passive upper airway collapsibility during propofol anesthesia. Method Twenty male subjects were studied, randomized to one of two experimental groups: fixed-jaw or free-jaw. Propofol infusion was used for induction and to maintain blood at a constant target concentration between 1.5 and 2.0 μg/ml. Nasal mask pressure (PN) was intermittently reduced to evaluate the upper airway collapsibility (passive PCRIT) and upstream resistance (RUS) at each level of head elevation (0, 3, 6, and 9 cm). The authors measured the Frankfort plane (head flexion) and the mandible plane (jaw opening) angles at each level of head elevation. Analysis of variance was used to determine the effect of head elevation on PCRIT, head flexion, and jaw opening within each group. Results In both groups the Frankfort plane and mandible plane angles increased with head elevation (P &lt; 0.05), although the mandible plane angle was smaller in the free-jaw group (i.e., increased jaw opening). In the fixed-jaw group, head elevation decreased upper airway collapsibility (PCRIT ~ -7 cm H₂O at greater than 6 cm elevation) compared with the baseline position (PCRIT ~ -3 cm H₂O at 0 cm elevation; P &lt; 0.05). Conclusion : Elevating the head position by 6 cm while ensuring mouth closure (centric occlusion) produces substantial decreases in upper airway collapsibility and maintains upper airway patency during anesthesia.

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