5-HT at hypoglossal motor nucleus and respiratory control of genioglossus muscle in anesthetized rats

Neuromodulator interdependence posits that changes in one or more neuromodulators are compensated by changes in other modulators to maintain stability in the respiratory control network. Herein, we studied compensatory neuromodulation in the hypoglossal motor nucleus (HMN) after chronic implantation of microtubules unilaterally ( n = 5) or bilaterally ( n = 5) into the HMN. After recovery, receptor agonists or antagonists in mock cerebrospinal fluid (mCSF) were dialyzed during the awake and non-rapid eye movement (NREM) sleep states. During day studies, dialysis of the µ-opioid inhibitory receptor agonist [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO; 100 µM) decreased pulmonary ventilation (V̇i), breathing frequency ( f), and genioglossus (GG) muscle activity but did not alter neuromodulators measured in the effluent mCSF. However, neither unilateral dialysis of a broad spectrum muscarinic receptor antagonist (atropine; 50 mM) nor unilateral or bilateral dialysis of a mixture of excitatory receptor antagonists altered V̇i or GG activity, but all of these did increase HMN serotonin (5-HT) levels. Finally, during night studies, DAMGO and excitatory receptor antagonist decreased ventilatory variables during NREM sleep but not during wakefulness. These findings contrast with previous dialysis studies in the ventral respiratory column (VRC) where unilateral DAMGO or atropine dialysis had no effects on breathing and bilateral DAMGO or unilateral atropine increased V̇i and f and decreased GABA or increased 5-HT, respectively. Thus we conclude that the mechanisms of compensatory neuromodulation are less robust in the HMN than in the VRC under physiological conditions in adult goats, possibly because of site differences in the underlying mechanisms governing neuromodulator release and consequently neuronal activity, and/or responsiveness of receptors to compensatory neuromodulators. NEW & NOTEWORTHY Activation of inhibitory µ-opioid receptors in the hypoglossal motor nucleus decreased ventilation under physiological conditions and did not affect neurochemicals in effluent dialyzed mock cerebral spinal fluid. These findings contrast with studies in the ventral respiratory column where unilateral [d-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO) had no effects on ventilation and bilateral DAMGO or unilateral atropine increased ventilation and decreased GABA or increased serotonin, respectively. Our data support the hypothesis that mechanisms that govern local compensatory neuromodulation within the brain stem are site specific under physiological conditions.

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Postnatal developmental expressions of neurotransmitters and receptors in various brain stem nuclei of rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.01301.2004 ◽

2005 ◽

Vol 98 (4) ◽

pp. 1442-1457 ◽

Cited By ~ 74

Author(s):

Qiuli Liu ◽

Margaret T. T. Wong-Riley

Keyword(s):

Brain Stem ◽

Respiratory Control ◽

Nucleus Ambiguus ◽

Hypoglossal Nucleus ◽

Motor Nucleus ◽

Developmental Trend ◽

Receptor Subunit ◽

Cuneate Nucleus ◽

Glycine Receptors ◽

Dorsal Motor Nucleus

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3–4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-d-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3–4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Bötzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.

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Reduced genioglossus muscle activity caused by fluid overload in anesthetized rats

Physiological Reports ◽

10.14814/phy2.14445 ◽

2020 ◽

Vol 8 (13) ◽

Author(s):

Parisa Sabetian ◽

Azadeh Yadollahi ◽

Paul B. Yoo

Keyword(s):

Muscle Activity ◽

Fluid Overload ◽

Genioglossus Muscle ◽

Anesthetized Rats

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The Respiratory Phenotype of Pompe Disease Rodent Models

10.20944/preprints202001.0256.v1 ◽

2020 ◽

Author(s):

Anna Fusco ◽

Angela McCall ◽

Justin Dhindsa ◽

Lucy Zheng ◽

Aidan Bailey ◽

...

Keyword(s):

Pompe Disease ◽

Neuromuscular Junctions ◽

Respiratory Control ◽

Glycogen Storage ◽

Motor Nucleus ◽

Rodent Models ◽

Respiratory Dysfunction ◽

Glycogen Accumulation ◽

Search Terms ◽

Respiratory Pathology

Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA) – a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease rodent models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts which characterize the respiratory phenotype of Pompe rodent models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease rodent models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, phrenic and hypoglossal motor nucleus, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle and higher order respiratory control centers. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.

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Respiratory activation of the genioglossus muscle involves both non-NMDA and NMDA glutamate receptors at the hypoglossal motor nucleus in vivo

Neuroscience ◽

10.1016/j.neuroscience.2005.12.040 ◽

2006 ◽

Vol 138 (4) ◽

pp. 1407-1424 ◽

Cited By ~ 32

Author(s):

H.W. Steenland ◽

H. Liu ◽

S. Sood ◽

X. Liu ◽

R.L. Horner

Keyword(s):

Glutamate Receptors ◽

Motor Nucleus ◽

Genioglossus Muscle ◽

Nmda Glutamate Receptors

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Development of thyrotropin-releasing hormone and norepinephrine potentiation of inspiratory-related hypoglossal motoneuron discharge in neonatal and juvenile mice in vitro

Journal of Neurophysiology ◽

10.1152/jn.1994.72.5.2538 ◽

1994 ◽

Vol 72 (5) ◽

pp. 2538-2541 ◽

Cited By ~ 82

Author(s):

G. D. Funk ◽

J. C. Smith ◽

J. L. Feldman

Keyword(s):

Motor Nerve ◽

Age Groups ◽

Respiratory Control ◽

Upper Airway ◽

Thyrotropin Releasing Hormone ◽

Motor Nucleus ◽

Releasing Hormone ◽

Hypoglossal Motoneuron ◽

Burst Amplitude

1. The ontogeny of thyrotropin-releasing hormone (TRH) and norepinephrine (NE) potentiation of inspiratory-related hypoglossal (XII) motor nerve discharge was studied in medullary slices from P0–3, P7, and P11-14 mice that retain functional networks for respiration. 2. TRH, applied locally to the XII motor nucleus, had no effect on XII inspiratory burst amplitude in slices from P0–3 mice. By P7 there was significant potentiation of burst amplitude that increased more than three-fold by P11–14. NE applied to the XII nucleus produced significant potentiation in all age groups. Potentiation increased developmentally with the largest increase occurring between P0–3 and P7. 3. Thus catecholamine and TRH modulation of inspiratory-related XII nerve activity increases during the first two weeks of life; the potentiating effects of NE appear prior to those of TRH. 4. With rhythmically active, transverse medullary slices from mice up to 2 wk of age, it is now possible to study the development of XII motoneuron modulation as it relates to respiratory control of the upper airway.

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GABAA receptor antagonism at the hypoglossal motor nucleus increases genioglossus muscle activity in NREM but not REM sleep

The Journal of Physiology ◽

10.1113/jphysiol.2002.033696 ◽

2003 ◽

Vol 548 (2) ◽

pp. 569-583 ◽

Cited By ~ 61

Author(s):

J. L Morrison ◽

S. Sood ◽

H. Liu ◽

E. Park ◽

P. Nolan ◽

...

Keyword(s):

Gabaa Receptor ◽

Rem Sleep ◽

Muscle Activity ◽

Motor Nucleus ◽

Genioglossus Muscle ◽

Receptor Antagonism

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Glycine at hypoglossal motor nucleus: genioglossus activity, CO2 responses, and the additive effects of GABA

Journal of Applied Physiology ◽

10.1152/japplphysiol.00464.2002 ◽

2002 ◽

Vol 93 (5) ◽

pp. 1786-1796 ◽

Cited By ~ 28

Author(s):

Janna L. Morrison ◽

Sandeep Sood ◽

Xia Liu ◽

Hattie Liu ◽

Eileen Park ◽

...

Keyword(s):

Receptor Agonist ◽

Respiratory Control ◽

Motor Nucleus ◽

Additive Effects ◽

Rapid Eye Movement Sleep ◽

Hypoglossal Motoneurons ◽

Artificial Cerebrospinal Fluid ◽

Respiratory Stimulation

There is evidence for glycine and GABAA-receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo, and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. This study tests the hypotheses that glycine at the hypoglossal motor nucleus (HMN) will suppress genioglossus (GG) muscle activity, even in the presence of hypercapnic respiratory stimulation, and the effects of glycine will be blocked by strychnine. We also determined whether coapplication of glycine and muscimol (GABAA- receptor agonist) to the HMN is additive in suppressing GG activity. Twenty-four urethane-anesthetized, tracheotomized, and vagotomized rats were studied. Diaphragm and GG activities, the electroencephalogram, and blood pressure were recorded. Microdialysis probes were implanted into the HMN for delivery of artificial cerebrospinal fluid (control), glycine (0.0001–10 mM), or muscimol (0.1 μM). Increasing glycine at the HMN produced graded suppression of GG activity ( P < 0.001), although the GG still responded to stimulation with 7% inspired CO2( P = 0.002). Strychnine (0.1 mM) reversed the glycine-mediated suppression of GG activity, whereas combined glycine and muscimol were additive in GG muscle suppression. It remains to be determined whether the recruitment of such glycine and GABA mechanisms explains the periods of major GG suppression in behaviors such as rapid eye movement sleep.

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Role of the Kölliker-Fuse nucleus in cardiovascular responses to hypoxia and baroreceptor activation in anesthetized rats

Bioimpacts ◽

10.15171/bi.2020.07 ◽

2019 ◽

Vol 10 (1) ◽

pp. 55-61

Author(s):

Nafiseh Mirzaei-Damabi ◽

Bahar Rostami ◽

Masoumeh Hatam

Keyword(s):

Intravenous Injection ◽

Significant Role ◽

Cardiovascular Effect ◽

Respiratory Control ◽

Cardiovascular Responses ◽

Anesthetized Rats ◽

Systemic Hypoxia ◽

Induced Hypertension ◽

Baroreceptor Activation

Introduction: Parabrachial Kölliker-Fuse (KF) complex, located in dorsolateral part of the pons, is involved in the respiratory control, however, its role in the baroreflex and chemoreflex responses has not been established yet. This study was performed to test the contribution of the KF to chemoreflex and baroreflex and the effect of microinjection of a reversible synaptic blocker (Cocl2) into the KF in urethane anesthetized rats. Methods: Activation of chemoreflex was induced by systemic hypoxia caused by N2 breathing for 30 seconds "hypoxic- hypoxia methods" and baroreflex was evoked by intravenous injection (i.v.) of phenylephrine (Phe, 20 µg /kg/0.05–0.1 mL). N2 induced generalized vasodilatation followed by tachycardia reflex and Phe evoked vasoconstriction followed by bradycardia. Results: Microinjection of Cocl2 (5 mM/100 nL/side) produced no significant changes in the Phe-induced hypertension and bradycardia, whereas the cardiovascular effect of N2 was significantly attenuated by the injection of CoCl2 to the KF. Conclusion: The KF played no significant role in the baroreflex, but could account for cardiovascular chemoreflex in urethane anesthetized rats.

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