To see the other types of publications on this topic, follow the link: Brainstem hypoglossal motoneurons.
Journal articles on the topic 'Brainstem hypoglossal motoneurons'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 25 journal articles for your research on the topic 'Brainstem hypoglossal motoneurons.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Cifra, Alessandra, Francesca Nani, Elina Sharifullina, and Andrea Nistri. "A repertoire of rhythmic bursting produced by hypoglossal motoneurons in physiological and pathological conditions." Philosophical Transactions of the Royal Society B: Biological Sciences 364, no. 1529 (September 12, 2009): 2493–500. http://dx.doi.org/10.1098/rstb.2009.0071.
Full textAbstract:
The brainstem nucleus hypoglossus contains motoneurons that provide the exclusive motor nerve supply to the tongue. In addition to voluntary tongue movements, tongue muscles rhythmically contract during a wide range of physiological activities, such as respiration, swallowing, chewing and sucking. Hypoglossal motoneurons are destroyed early in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease often associated with a deficit in the transport system of the neurotransmitter glutamate. The present study shows how periodic electrical discharges of motoneurons are mainly produced by a neuronal network that drives them into bursting mode via glutamatergic excitatory synapses. Burst activity is, however, modulated by the intrinsic properties of motoneurons that collectively synchronize their discharges via gap junctions to create ‘group bursters’. When glial uptake of glutamate is blocked, a distinct form of pathological bursting spontaneously emerges and leads to motoneuron death. Conversely, H 2 O 2 -induced oxidative stress strongly increases motoneuron excitability without eliciting bursting. Riluzole (the only drug currently licensed for the treatment of ALS) suppresses bursting of hypoglossal motoneurons caused by blockage of glutamate uptake and limits motoneuron death. These findings highlight how different patterns of electrical oscillations of brainstem motoneurons underpin not only certain physiological activities, but also motoneuron death induced by glutamate transporter impairment.
2
Silva-Hucha, Silvia, Angel M. Pastor, and Sara Morcuende. "Neuroprotective Effect of Vascular Endothelial Growth Factor on Motoneurons of the Oculomotor System." International Journal of Molecular Sciences 22, no. 2 (January 15, 2021): 814. http://dx.doi.org/10.3390/ijms22020814.
Full textAbstract:
Vascular endothelial growth factor (VEGF) was initially characterized as a potent angiogenic factor based on its activity on the vascular system. However, it is now well established that VEGF also plays a crucial role as a neuroprotective factor in the nervous system. A deficit of VEGF has been related to motoneuronal degeneration, such as that occurring in amyotrophic lateral sclerosis (ALS). Strikingly, motoneurons of the oculomotor system show lesser vulnerability to neurodegeneration in ALS compared to other motoneurons. These motoneurons presented higher amounts of VEGF and its receptor Flk-1 than other brainstem pools. That higher VEGF level could be due to an enhanced retrograde input from their target muscles, but it can also be produced by the motoneurons themselves and act in an autocrine way. By contrast, VEGF’s paracrine supply from the vicinity cells, such as glial cells, seems to represent a minor source of VEGF for brainstem motoneurons. In addition, ocular motoneurons experiment an increase in VEGF and Flk-1 level in response to axotomy, not observed in facial or hypoglossal motoneurons. Therefore, in this review, we summarize the differences in VEGF availability that could contribute to the higher resistance of extraocular motoneurons to injury and neurodegenerative diseases.
3
Robinson, David W., and William E. Cameron. "Time-Dependent Changes in Input Resistance of Rat Hypoglossal Motoneurons Associated with Whole-Cell Recording." Journal of Neurophysiology 83, no. 5 (May 1, 2000): 3160–64. http://dx.doi.org/10.1152/jn.2000.83.5.3160.
Full textAbstract:
The effect of cellular dialysis associated with whole-cell recording was studied in 24 developing hypoglossal motoneurons in a rat brainstem slice preparation. In all cases, establishing whole-cell continuity with the electrode solution resulted in an increase in the input resistance measured in current clamp. The mean magnitude of this increase was 39.7% and the time course of the maximum effect was quite variable. There was no correlation found between the time to maximum effect and the magnitude of the increase in resistance. These data indicate that the passive membrane properties are not constant during whole-cell recording in mammalian motoneurons.
4
Sawczuk, A., and K. M. Mosier. "Neural Control of Tongue Movement With Respect To Respiration and Swallowing." Critical Reviews in Oral Biology & Medicine 12, no. 1 (January 2001): 18–37. http://dx.doi.org/10.1177/10454411010120010101.
Full textAbstract:
The tongue must move with remarkable speed and precision between multiple orofacial motor behaviors that are executed virtually simultaneously. Our present understanding of these highly integrated relationships has been limited by their complexity. Recent research indicates that the tongue's contribution to complex orofacial movements is much greater than previously thought. The purpose of this paper is to review the neural control of tongue movement and relate it to complex orofacial behaviors. Particular attention will be given to the interaction of tongue movement with respiration and swallowing, because the morbidity and mortality associated with these relationships make this a primary focus of many current investigations. This review will begin with a discussion of peripheral tongue muscle and nerve physiology that will include new data on tongue contractile properties. Other relevant peripheral oral cavity and oropharyngeal neurophysiology will also be discussed. Much of the review will focus on brainstem control of tongue movement and modulation by neurons that control swallowing and respiration, because it is in the brainstem that orofacial motor behaviors sort themselves out from their common peripheral structures. There is abundant evidence indicating that the neural control of protrusive tongue movement by motoneurons in the ventral hypoglossal nucleus is modulated by respiratory neurons that control inspiratory drive. Yet, little is known of hypoglossal motoneuron modulation by neurons controlling swallowing or other complex movements. There is evidence, however, suggesting that functional segregation of respiration and swallowing within the brainstem is reflected in somatotopy within the hypoglossal nucleus. Also, subtle changes in the neural control of tongue movement may signal the transition between respiration and swallowing. The final section of this review will focus on the cortical integration of tongue movement with complex orofacial movements. This section will conclude with a discussion of the functional and clinical significance of cortical control with respect to recent advances in our understanding of the peripheral and brainstem physiology of tongue movement.
5
Powell, Gregory L., Richard B. Levine, Amanda M. Frazier, and Ralph F. Fregosi. "Influence of developmental nicotine exposure on spike-timing precision and reliability in hypoglossal motoneurons." Journal of Neurophysiology 113, no. 6 (March 15, 2015): 1862–72. http://dx.doi.org/10.1152/jn.00838.2014.
Full textAbstract:
Smoothly graded muscle contractions depend in part on the precision and reliability of motoneuron action potential generation. Whether or not a motoneuron generates spikes precisely and reliably depends on both its intrinsic membrane properties and the nature of the synaptic input that it receives. Factors that perturb neuronal intrinsic properties and/or synaptic drive may compromise the temporal precision and the reliability of action potential generation. We have previously shown that developmental nicotine exposure (DNE) alters intrinsic properties and synaptic transmission in hypoglossal motoneurons (XIIMNs). Here we show that the effects of DNE also include alterations in spike-timing precision and reliability, and spike-frequency adaptation, in response to sinusoidal current injection. Current-clamp experiments in brainstem slices from neonatal rats show that DNE lowers the threshold for spike generation but increases the variability of spike-timing mechanisms. DNE is also associated with an increase in spike-frequency adaptation and reductions in both peak and steady-state firing rate in response to brief, square wave current injections. Taken together, our data indicate that DNE causes significant alterations in the input-output efficiency of XIIMNs. These alterations may play a role in the increased frequency of obstructive apneas and altered suckling strength and coordination observed in nicotine-exposed neonatal humans.
6
Allain, Anne-Emilie, Hervé Le Corronc, Alain Delpy, William Cazenave, Pierre Meyrand, Pascal Legendre, and Pascal Branchereau. "Maturation of the GABAergic Transmission in Normal and Pathologic Motoneurons." Neural Plasticity 2011 (2011): 1–13. http://dx.doi.org/10.1155/2011/905624.
Full textAbstract:
γ-aminobutyric acid (GABA) acting on Cl−-permeable ionotropic type A (GABAA) receptors (GABAAR) is the major inhibitory neurotransmitter in the adult central nervous system of vertebrates. In immature brain structures, GABA exerts depolarizing effects mostly contributing to the expression of spontaneous activities that are instructive for the construction of neural networks but GABA also acts as a potent trophic factor. In the present paper, we concentrate on brainstem and spinal motoneurons that are largely targeted by GABAergic interneurons, and we bring together data on the switch from excitatory to inhibitory effects of GABA, on the maturation of the GABAergic system and GABAAR subunits. We finally discuss the role of GABA and its GABAAR in immature hypoglossal motoneurons of the spastic (SPA) mouse, a model of human hyperekplexic syndrome.
7
Nakajima, Misuzu. "Brainstem Segmental Arrangement of Sucking Rhythm Generators for Trigeminal, Facial and Hypoglossal Motoneurons." JOURNAL OF THE STOMATOLOGICAL SOCIETY,JAPAN 66, no. 1 (1999): 88–97. http://dx.doi.org/10.5357/koubyou.66.88.
Full text
8
Fietkiewicz, Christopher, Kenneth A. Loparo, and Christopher G. Wilson. "Drive latencies in hypoglossal motoneurons indicate developmental change in the brainstem respiratory network." Journal of Neural Engineering 8, no. 6 (October 1, 2011): 065011. http://dx.doi.org/10.1088/1741-2560/8/6/065011.
Full text
9
Komarov, M., M. Naji, G. Krishnan, A. Malhotra, F. Powell, I. Rukhadze, V. Fenik, and M. Bazhenov. "0139 COMPUTATIONAL MODEL OF BRAINSTEM CIRCUIT FOR STATE-DEPENDENT CONTROL OF HYPOGLOSSAL MOTONEURONS." Sleep 40, suppl_1 (April 28, 2017): A52. http://dx.doi.org/10.1093/sleepj/zsx050.138.
Full text
10
Lape, Remigijus, and Andrea Nistri. "Characteristics of fast Na+current of hypoglossal motoneurons in a rat brainstem slice preparation." European Journal of Neuroscience 13, no. 4 (February 2001): 763–72. http://dx.doi.org/10.1046/j.0953-816x.2000.01433.x.
Full text
11
Tadros, M. A., K. E. Farrell, P. R. Schofield, A. M. Brichta, B. A. Graham, A. J. Fuglevand, and R. J. Callister. "Intrinsic and synaptic homeostatic plasticity in motoneurons from mice with glycine receptor mutations." Journal of Neurophysiology 111, no. 7 (April 1, 2014): 1487–98. http://dx.doi.org/10.1152/jn.00728.2013.
Full textAbstract:
Inhibitory synaptic inputs to hypoglossal motoneurons (HMs) are important for modulating excitability in brainstem circuits. Here we ask whether reduced inhibition, as occurs in three murine mutants with distinct naturally occurring mutations in the glycine receptor (GlyR), leads to intrinsic and/or synaptic homeostatic plasticity. Whole cell recordings were obtained from HMs in transverse brainstem slices from wild-type ( wt), spasmodic ( spd), spastic ( spa), and oscillator ( ot) mice (C57Bl/6, approximately postnatal day 21). Passive and action potential (AP) properties in spd and ot HMs were similar to wt. In contrast, spa HMs had lower input resistances, more depolarized resting membrane potentials, higher rheobase currents, smaller AP amplitudes, and slower afterhyperpolarization current decay times. The excitability of HMs, assessed by “gain” in injected current/firing-frequency plots, was similar in all strains whereas the incidence of rebound spiking was increased in spd. The difference between recruitment and derecruitment current (i.e., Δ I) for AP discharge during ramp current injection was more negative in spa and ot. GABAA miniature inhibitory postsynaptic current (mIPSC) amplitude was increased in spa and ot but not spd, suggesting diminished glycinergic drive leads to compensatory adjustments in the other major fast inhibitory synaptic transmitter system in these mutants. Overall, our data suggest long-term reduction in glycinergic drive to HMs results in changes in intrinsic and synaptic properties that are consistent with homeostatic plasticity in spa and ot but not in spd. We propose such plasticity is an attempt to stabilize HM output, which succeeds in spa but fails in ot.
12
Horner, Richard L. "Emerging principles and neural substrates underlying tonic sleep-state-dependent influences on respiratory motor activity." Philosophical Transactions of the Royal Society B: Biological Sciences 364, no. 1529 (September 12, 2009): 2553–64. http://dx.doi.org/10.1098/rstb.2009.0065.
Full textAbstract:
Respiratory muscles with dual respiratory and non-respiratory functions (e.g. the pharyngeal and intercostal muscles) show greater suppression of activity in sleep than the diaphragm, a muscle almost entirely devoted to respiratory function. This sleep-related suppression of activity is most apparent in the tonic component of motor activity, which has functional implications of a more collapsible upper airspace in the case of pharyngeal muscles, and decreased functional residual capacity in the case of intercostal muscles. A major source of tonic drive to respiratory motoneurons originates from neurons intimately involved in states of brain arousal, i.e. neurons not classically involved in generating respiratory rhythm and pattern per se . The tonic drive to hypoglossal motoneurons, a respiratory motor pool with both respiratory and non-respiratory functions, is mediated principally by noradrenergic and glutamatergic inputs, these constituting the essential components of the wakefulness stimulus . These tonic excitatory drives are opposed by tonic inhibitory glycinergic and γ-amino butyric acid (GABA) inputs that constrain the level of respiratory-related motor activity, with the balance determining net motor tone. In sleep, the excitatory inputs are withdrawn and GABA release into the brainstem is increased, thus decreasing respiratory motor tone and predisposing susceptible individuals to hypoventilation and obstructive sleep apnoea.
13
Poliacek, I., M. Simera, V. Calkovsky, and J. Jakus. "Upper Airway Control in Airway Defense." Acta Medica Martiniana 16, no. 1 (April 1, 2016): 5–16. http://dx.doi.org/10.1515/acm-2016-0001.
Full textAbstract:
AbstractUpper airways (UA) are an organic component of the respiratory tract, they serve to respiration, respiratory tract protection and defense, phonation, deglutition, etc. The functions of UA are regulated by motor control of the oral, pharyngeal, and laryngeal muscles.UA typically stiffen and widen during inspiration mainly due to the activation of the alae nasi, genioglossus m., pharyngeal dilators, and laryngeal abductors. These and other UA muscles (e.g. laryngeal and pharyngeal constrictors) may express varoius activity patterns, actively shaping UA depending on species, arousal, respiratory drive, and behavior being executed. E.g. during coughing and sneezing laryngeal movement consists of abductions in inspiration and expiration and adductions in compression and subsequent constriction phase. The cricopharyngeus m., in cough expiration the superior pharyngeal constrictor and in the sneeze expiration the styloglossus and levator veli palatini m. are activated. Unlike in breathing or coughing, where UA serve to respiration-protection-defense, the pharyngeal phase of swallowing is essentially made by the coordinated action of a number of UA muscles.Motoneurons driving the UA muscles are located primarily in the hypoglossal and ambigual nuclei. Motor pattern of individual motoneuronal pools is determined by activation-inhibition-modulation from pre-motoneurons and other upstream neurons of the reflex circuits. Laryngeal and hypoglossal nerve activity is during breathing under command of respiratory central pattern generator. UA muscles are driven in inspiration primarily from augmenting, less from decrementing and constant inspiratory neurons. Number of additional inputs is involved in UA regulation during expirations and other motor behaviors. Anatomical and functional studies pointed out number of brainstem areas, such as the regions of solitary tract nucleus, hypoglossal ncl., trigeminal ncl., lateral tegmental field, raphé, the ventral and ventrolateral medulla, pontine parabrachial region, etc. with neurons related to UA motor control.Abundant connectivity of the neuronal network that controls UA patency employs almost all kind of receptors and neurotransmitter/neuromodulator systems. Among large number of diseases and disorders that relate to UA, primarily cholinergic, norepinephrine, and serotonergic tonic drives are implicated in those resulted from the reduced UA tone. Pharmacological and frequently simple surgical interventions may improve these conditions (snore, obturation) in patients. Recently, besides medicinal treatment, conditional procedures incorporating an exercise and practice, stimulation of appropriate afferent pathways, and combining reflex responses may offer promising therapies.
14
Bayliss, D. A., F. Viana, and A. J. Berger. "Mechanisms underlying excitatory effects of thyrotropin-releasing hormone on rat hypoglossal motoneurons in vitro." Journal of Neurophysiology 68, no. 5 (November 1, 1992): 1733–45. http://dx.doi.org/10.1152/jn.1992.68.5.1733.
Full textAbstract:
1. The hypoglossal motor nucleus contains binding sites for the neuropeptide thyrotropin-releasing hormone (TRH) and is innervated by TRH-containing fibers. Although excitatory effects of TRH on hypoglossal motoneurons (HMs) have been described, the ionic mechanisms by which TRH exerts such effects have not been fully elucidated. Therefore, we investigated the effects of TRH on HMs in transverse slices of rat brainstem with intracellular recording techniques. 2. TRH was applied by perfusion (0.1-10 microM) or by pressure ejection (1.0 microM), while HMs were recorded in current or voltage clamp. In all cells tested, TRH caused a depolarization and/or the development of an inward current. These effects were fully reversible, dose dependent, and showed only modest desensitization with long applications. In addition, although TRH increased synaptic activity in many cells, the depolarizing response to TRH was maintained in tetrodotoxin (0.5-1.0 microM)-containing or in a nominally Ca(2+)-free perfusate containing 2 mM Mn2+. Thus TRH acts directly on HMs to cause the depolarization. 3. Hyperpolarizing current (or voltage) steps superimposed on the TRH-induced depolarization (or inward current) revealed a decreased input conductance. Extrapolated instantaneous current-voltage relationships obtained before and at the peak of the response to TRH intersected (i.e., reversed) at -101 mV, negative to the expected K+ equilibrium potential (EK). When extracellular [K+] was raised from 3 to 12 mM, the reversal potential was shifted in the depolarizing direction and the magnitude of the TRH-induced depolarization was diminished. Moreover, the TRH response was enhanced in size from depolarized potentials (i.e., further from EK). Taken together, these results indicate that TRH depolarizes HMs, in part, by decreasing a resting K+ conductance. 4. Similar to TRH, bath-application of 2 mM Ba2+ caused a depolarization associated with decreased conductance, suggesting that Ba2+ also blocks a resting K+ conductance. The Ba(2+)-sensitive and TRH-sensitive resting K+ conductances are apparently identical; in the presence of Ba2+, the customary TRH-induced decrease in conductance was occluded. 5. It is noteworthy that the TRH-induced inward current (ITRH), although diminished, was not entirely blocked by Ba2+. This second Ba(2+)-insensitive component of ITRH was not associated with a measurable change in input conductance. It was especially evident during current-clamp recordings, when the diminutive TRH-induced current was still capable of causing a substantial depolarization. The ionic basis of the residual TRH-induced inward current remains to be determined. 6. We investigated the functional consequences of these mechanisms of action of TRH on spike firing behavior of HMs.(ABSTRACT TRUNCATED AT 400 WORDS)
15
Katakura, N. "Rhythmic membrane potential changes of hypoglossal motoneurons during NMDA-induced sucking-like activity in an en bioc brainstem preparations isolated from newborn mice." Neuroscience Research 38 (2000): S150. http://dx.doi.org/10.1016/s0168-0102(00)81750-2.
Full text
16
Guntinas-Lichius, Orlando, Gregor Hundeshagen, Thomas Paling, and Doychin N. Angelov. "IMPACT OF DIFFERENT TYPES OF FACIAL NERVE RECONSTRUCTION ON THE RECOVERY OF MOTOR FUNCTION." Neurosurgery 61, no. 6 (December 1, 2007): 1276–85. http://dx.doi.org/10.1227/01.neu.0000306107.70421.a4.
Full textAbstract:
Abstract OBJECTIVE Poor functional recovery after facial nerve reconstruction is characterized by mass movements and synkinesis. Major reasons are axonal sprouting from the regenerating axons leading to misdirected reinnervation and hyperinnervation as well as polyinnervation of the mimic muscle end plates. We analyzed whether or not the type of nerve reconstruction influenced these pathological phenomena. METHODS The experiments were performed on 48 adult rats divided into four groups. One group served as an intact control and the experimental groups were subjected to facial-facial nerve repair (FFN), facial nerve interpositional grafting, and hypoglossal-facial nerve repair (HFN), with 12 subjects in each group. Two months later, functional recovery was measured by biometrical motion analysis of whisking. Retrograde fluorescence labeling of the brainstem motoneurons was used to quantify the degree of collateral axonal branching at the lesion site. Fluorescence histochemistry of sections through the levator labii superioris muscle was performed to quantify the degree of polyinnervation after surgery. RESULTS The type of nerve reconstruction significantly influenced the regeneration. The whisking amplitude did not recover completely regardless of the type of reconstruction. The angular velocity and angular acceleration of the vibrissal hairs showed a full recovery after facial nerve interpositional grafting and HFN, whereas these parameters remained decreased after FFN. Significantly less collateral branching and polyinnervation of the end plates were determined after grafting and HFN than after FFN. CONCLUSION No type of immediate facial nerve reconstruction results in a full recovery in the rat. However, the morphological and functional recovery was significantly better after grafting and HFN than after FFN.
17
Donga, R., and J. P. Lund. "Discharge patterns of trigeminal commissural last-order interneurons during fictive mastication in the rabbit." Journal of Neurophysiology 66, no. 5 (November 1, 1991): 1564–78. http://dx.doi.org/10.1152/jn.1991.66.5.1564.
Full textAbstract:
1. The aim of these experiments was to examine the physiological properties and patterns of firing of trigeminal interneurons during fictive mastication in anesthetized and paralyzed rabbits. Antidromic stimulation was used to show that the 82 interneurons projected to the area of the contralateral fifth nerve motor nucleus (NVmot). 2. Straight-line conduction velocities calculated from stereotaxic coordinates of the stimulating and recording electrodes for 63 interneurons were found to range between 3.7 and 16.3 m/s (mean, 9.5 m/s). 3. Histological reconstructions of recording electrode tracks showed that the interneurons observed in this study were located in the lateral brain stem in or just medial to the rostral trigeminal sensory nuclei, including the intertrigeminal (NVint) and supratrigeminal (NVs) areas, the main sensory nucleus of the fifth nerve (NVsnpr), the rostral subdivision of the oral nucleus of the spinal trigeminal tract (NVor tau), and the rostral part of the parvocellular reticular nucleus (NRpc alpha). 4. Forty-six interneurons were shown to have low-threshold (LT) peripheral receptive fields, and 41 of these (88%) were in the oral cavity. Most of the responses were rapidly adapting. 5. Twenty-eight interneurons changed their pattern of firing during cortically induced fictive mastication. The discharge frequency of 20 neurons varied in phase with the fictive masticatory motor output, which was recorded from central ends of cut hypoglossal nerves (XII) and/or from the NVmot. Others were briefly excited and then inhibited (n = 2), only inhibited (n = 4), or tonically excited during fictive mastication (n = 2). Fifteen others were unaffected by this test. 6. It was found that the rhythmically active neurons could be further subdivided into two categories: those receiving short-latency excitatory input from the masticatory area of the cortex (n = 11) and those that did not (n = 9). No obvious differences in peripheral receptive fields for neurons in these categories were found. 7. We suggest that these phasically active premotor neurons are part of the circuitry generating the rhythmic masticatory pattern, specifically those that directly control the bursts of firing of the trigeminal motoneurons (burst generators, BGs). Their properties allow them to integrate sensory information and descending commands with the masticatory rhythm that is probably generated in midline brainstem reticular nuclei.
18
Katakura, Nobuo, Lia Jia, and Yoshio Nakamura. "NMDA-induced rhythmical activities of the hypoglossal motoneuron in an in vitro brainstem-spinal cord preparation from newborn rats." Neuroscience Research Supplements 19 (January 1994): S176. http://dx.doi.org/10.1016/0921-8696(94)92762-6.
Full text
19
Jampolska, Monika, Kryspin Andrzejewski, Małgorzata Zaremba, Ilona Joniec-Maciejak, and Katarzyna Kaczyńska. "Deficiency of Biogenic Amines Modulates the Activity of Hypoglossal Nerve in the Reserpine Model of Parkinson’s Disease." Cells 10, no. 3 (March 2, 2021): 531. http://dx.doi.org/10.3390/cells10030531.
Full textAbstract:
The underlying cause of respiratory impairments appearing in Parkinson’s disease (PD) is still far from being elucidated. To better understand the pathogenesis of respiratory disorders appearing in PD, we studied hypoglossal (HG) and phrenic (PHR) motoneuron dysfunction in a rat model evoked with reserpine administration. After reserpine, a decrease in the baseline amplitude and minute HG activity was noted, and no depressive phase of the hypoxic ventilatory response was observed. The pre-inspiratory time of HG activity along with the ratio of pre-inspiratory time to total respiratory cycle time and the ratio of pre-inspiratory to inspiratory amplitude were significantly reduced during normoxia, hypoxia, and recovery compared to sham rats. We suggest that the massive depletion of not only dopamine, but above all noradrenaline and serotonin in the brainstem observed in our study, has an impact on the pre-inspiratory activity of the HG. The shortening of the pre-inspiratory activity of the HG in the reserpine model may indicate a serious problem with maintaining the correct diameter of the upper airways in the preparation phase for inspiratory effort and explain the development of obstructive sleep apnea in some PD patients. Therapies involving the supplementation of amine depletion other than dopamine should be considered.
20
Browe, Brigitte M., Ying-Jie Peng, Jayasri Nanduri, Nanduri R. Prabhakar, and Alfredo J. Garcia. "Gasotransmitter modulation of hypoglossal motoneuron activity." eLife 12 (January 19, 2023). http://dx.doi.org/10.7554/elife.81978.
Full textAbstract:
Obstructive sleep apnea (OSA) is characterized by sporadic collapse of the upper airway leading to periodic disruptions in breathing. Upper airway patency is governed by genioglossal nerve activity that originates from the hypoglossal motor nucleus. Mice with targeted deletion of the gene Hmox2, encoding the carbon monoxide (CO) producing enzyme, heme oxygenase-2 (HO-2), exhibit OSA, yet the contribution of central HO-2 dysregulation to the phenomenon is unknown. Using the rhythmic brainstem slice preparation that contains the preBötzinger complex (preBötC) and the hypoglossal nucleus, we tested the hypothesis that central HO-2 dysregulation weakens hypoglossal motoneuron output. Disrupting HO-2 activity increased the occurrence of subnetwork activity from the preBötC, which was associated with an increased irregularity of rhythmogenesis. These phenomena were also associated with the intermittent inability of the preBötC rhythm to drive output from the hypoglossal nucleus (i.e., transmission failures), and a reduction in the input-output relationship between the preBötC and the motor nucleus. HO-2 dysregulation reduced excitatory synaptic currents and intrinsic excitability in inspiratory hypoglossal neurons. Inhibiting activity of the CO-regulated H2S producing enzyme, cystathionine-g-lyase (CSE), reduced transmission failures in HO-2 null brainstem slices, which also normalized excitatory synaptic currents and intrinsic excitability of hypoglossal motoneurons. These findings demonstrate a hitherto uncharacterized modulation of hypoglossal activity through mutual interaction of HO‑2/CO and CSE/H2S, and support the potential importance of centrally‑derived gasotransmitter activity in regulating upper airway control.
21
Dergacheva, Olga, Thomaz Fleury-Curado, Vsevolod Y. Polotsky, Matthew Kay, Vivek Jain, and David Mendelowitz. "GABA and glycine neurons from the ventral medullary region inhibit hypoglossal motoneurons." Sleep 43, no. 6 (December 13, 2019). http://dx.doi.org/10.1093/sleep/zsz301.
Full textAbstract:
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.
22
Singer, Michele Lynn, Sabhya Rana, Ethan S. Benevides, Brian E. Barral, Barry J. Byrne, and David D. Fuller. "Chemogenetic activation of hypoglossal motoneurons in a mouse model of Pompe disease." Journal of Neurophysiology, August 17, 2022. http://dx.doi.org/10.1152/jn.00026.2022.
Full textAbstract:
Pompe disease is a lysosomal storage disease resulting from absence or deficiency of acid α-glucosidase (GAA). Tongue related disorders including dysarthria, dysphagia, and obstructive sleep apnea are common in Pompe disease. Our purpose was to determine if designer receptors exclusively activated by designer drugs (DREADDs) could be used to stimulate tongue motor output in a mouse model of Pompe disease. An adeno-associated virus serotype 9 (AAV9) encoding an excitatory DREADD (AAV9-hSyn-hM3D(Gq)-mCherry, 2.44 x 1010 vg) was administered to the posterior tongue of 5-7 week old Gaa null (Gaa-/-) mice. Lingual EMG responses to intraperitoneal injection of saline or a DREADD ligand (JHU37160-dihydrochloride, J60) were assessed 12 weeks later during spontaneous breathing. Saline injection produced no consistent changes in lingual EMG. Following the DREADD ligand, there were statistically significant (P<0.05) increases in both tonic and phasic inspiratory EMG activity recorded from the posterior tongue. Brainstem histology confirmed mCherry expression in hypoglossal (XII) motoneurons in all mice, thus verifying retrograde movement of the AAV9 vector. Morphologically, Gaa-/- XII motoneurons showed histologic characteristics that are typical of Pompe disease, including an enlarged soma and vacuolization. We conclude that lingual delivery of AAV9 can be used to drive functional expression of DREADD in XII motoneurons in a mouse model of Pompe disease.
23
Fenik, Victor B. "Revisiting Antagonist Effects in Hypoglossal Nucleus: Brainstem Circuit for the State-Dependent Control of Hypoglossal Motoneurons: A Hypothesis." Frontiers in Neurology 6 (December 1, 2015). http://dx.doi.org/10.3389/fneur.2015.00254.
Full text
24
Nógrádi, Bernát, Ádám Nyúl-Tóth, Mihály Kozma, Kinga Molnár, Roland Patai, László Siklós, Imola Wilhelm, and István A. Krizbai. "Upregulation of Nucleotide-Binding Oligomerization Domain-, LRR- and Pyrin Domain-Containing Protein 3 in Motoneurons Following Peripheral Nerve Injury in Mice." Frontiers in Pharmacology 11 (November 26, 2020). http://dx.doi.org/10.3389/fphar.2020.584184.
Full textAbstract:
Neuronal injuries are accompanied by release and accumulation of damage-associated molecules, which in turn may contribute to activation of the immune system. Since a wide range of danger signals (including endogenous ones) are detected by the nucleotide-binding oligomerization domain-, LRR- and pyrin domain-containing protein 3 (NLRP3) pattern recognition receptor, we hypothesized that NLRP3 may become activated in response to motor neuron injury. Here we show that peripheral injury of the oculomotor and the hypoglossal nerves results in upregulation of NLRP3 in corresponding motor nuclei in the brainstem of mice. Although basal expression of NLRP3 was observed in microglia, astroglia and neurons as well, its upregulation and co-localization with apoptosis-associated speck-like protein containing a caspase activation and recruitment domain, suggesting inflammasome activation, was only detected in neurons. Consequently, increased production of active pro-inflammatory cytokines interleukin-1β and interleukin-18 were detected after hypoglossal nerve axotomy. Injury-sensitive hypoglossal neurons responded with a more pronounced NLRP3 upregulation than injury-resistant motor neurons of the oculomotor nucleus. We further demonstrated that the mitochondrial protector diazoxide was able to reduce NLRP3 upregulation in a post-operative treatment paradigm. Our results indicate that NLRP3 is activated in motoneurons following acute nerve injury. Blockade of NLRP3 activation might contribute to the previously observed anti-inflammatory and neuroprotective effects of diazoxide.
25
García-Morales, Victoria, Ángela Gento-Caro, Federico Portillo, Fernando Montero, David González-Forero, and Bernardo Moreno-López. "Lysophosphatidic Acid and Several Neurotransmitters Converge on Rho-Kinase 2 Signaling to Manage Motoneuron Excitability." Frontiers in Molecular Neuroscience 14 (December 6, 2021). http://dx.doi.org/10.3389/fnmol.2021.788039.
Full textAbstract:
Intrinsic membrane excitability (IME) sets up neuronal responsiveness to synaptic drive. Several neurotransmitters and neuromodulators, acting through G-protein-coupled receptors (GPCRs), fine-tune motoneuron (MN) IME by modulating background K+ channels TASK1. However, intracellular partners linking GPCRs to TASK1 modulation are not yet well-known. We hypothesized that isoform 2 of rho-kinase (ROCK2), acting as downstream GPCRs, mediates adjustment of MN IME via TASK1. Electrophysiological recordings were performed in hypoglossal MNs (HMNs) obtained from adult and neonatal rats, neonatal knockout mice for TASK1 (task1–/–) and TASK3 (task3–/–, the another highly expressed TASK subunit in MNs), and primary cultures of embryonic spinal cord MNs (SMNs). Small-interfering RNA (siRNA) technology was also used to knockdown either ROCK1 or ROCK2. Furthermore, ROCK activity assays were performed to evaluate the ability of various physiological GPCR ligands to stimulate ROCK. Microiontophoretically applied H1152, a ROCK inhibitor, and siRNA-induced ROCK2 knockdown both depressed AMPAergic, inspiratory-related discharge activity of adult HMNs in vivo, which mainly express the ROCK2 isoform. In brainstem slices, intracellular constitutively active ROCK2 (aROCK2) led to H1152-sensitive HMN hyper-excitability. The aROCK2 inhibited pH-sensitive and TASK1-mediated currents in SMNs. Conclusively, aROCK2 increased IME in task3–/–, but not in task1–/– HMNs. MN IME was also augmented by the physiological neuromodulator lysophosphatidic acid (LPA) through a mechanism entailing Gαi/o-protein stimulation, ROCK2, but not ROCK1, activity and TASK1 inhibition. Finally, two neurotransmitters, TRH, and 5-HT, which are both known to increase MN IME by TASK1 inhibition, stimulated ROCK2, and depressed background resting currents via Gαq/ROCK2 signaling. These outcomes suggest that LPA and several neurotransmitters impact MN IME via Gαi/o/Gαq-protein-coupled receptors, downstream ROCK2 activation, and subsequent inhibition of TASK1 channels.