155 results on '"Long term facilitation"'
Search Results
2. Neural Network Reconfigurations: Changes of the Respiratory Network by Hypoxia as an Example
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Peña-Ortega, Fernando, COHEN, IRUN R., Series editor, LAJTHA, ABEL, Series editor, LAMBRIS, JOHN D., Series editor, PAOLETTI, RODOLFO, Series editor, REZAEI, NIMA, Series editor, von Bernhardi, Rommy, editor, Eugenín, Jaime, editor, and Muller, Kenneth J, editor
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- 2017
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- View/download PDF
3. Chronic Intermittent Hypoxia Blunts the Expression of Ventilatory Long Term Facilitation in Sleeping Rats
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Edge, Deirdre, O’Halloran, Ken D., Peers, Chris, editor, Kumar, Prem, editor, Wyatt, Christopher, editor, Gauda, Estelle, editor, Nurse, Colin A., editor, and Prabhakar, Nanduri, editor
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- 2015
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4. Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea.
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Alex, Raichel M., Panza, Gino S., Hakim, Huzaifa, Badr, M. Safwan, Edwards, Bradley A., Sands, Scott A., and Mateika, Jason H.
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CONTINUOUS positive airway pressure , *HYPOXEMIA , *SLEEP , *BODY mass index - Abstract
Key points: Repeated daily mild intermittent hypoxia has been endorsed as a therapy to promote the recovery of respiratory and limb motor dysfunction.One possible side‐effect of this therapy is an increase in apnoeic event number and duration, which is particularly relevant to participants with motor disorders coupled with an increased incidence of sleep apnoea.In this study, we report that increases in apnoeic event number and duration, following exposure to daily intermittent hypoxia, are the result of an increase in respiratory loop gain and the arousal threshold, in participants with obstructive sleep apnoea.Daily exposure to mild intermittent hypoxia also led to an increase in the ventilatory response to arousal.Accordingly, individuals with motor disorders receiving mild intermittent hypoxia as a therapy should be screened for the presence of sleep apnoea, and if present, administration of intermittent hypoxia during hours of wakefulness should be combined with continuous positive airway pressure treatment during sleep. We determined if exposure to mild intermittent hypoxia (MIH) causes an increase in loop gain (LG) and the arousal threshold (AT) during non‐rapid eye movement (NREM) sleep. Male participants with obstructive sleep apnoea (apnoea‐hypopnoea index > 5 events/h), matched for age, body mass index and race were divided into two groups (n = 13 in each group). Following a baseline sleep study, one group was exposed to twelve 4‐min episodes of hypoxia each day for 10 days and the other group to a sham protocol (SP). On Days 1 and 10, a sleep study was completed following exposure to MIH or the SP. For each sleep study, LG and the AT were measured during NREM sleep, using a model‐based approach, and expressed as a fraction of baseline measures. LG increased after exposure to MIH (Day 1: 1.11 ± 0.03, P = 0.002, Day 10: 1.17 ± 0.05, P = 0.001), but not after the SP (Day 1: 1.03 ± 0.04, P = 1.0, Day 10: 1.0 ± 0.02, P = 1.0). AT also increased after exposure to MIH (Day 1: 1.13 ± 0.05, P = 0.01, Day 10: 1.19 ± 0.08, P = 0.05) but not after the SP (Day 1: 1.04 ± 0.05, P = 0.6, Day 10: 0.96 ± 0.04, P = 1.0). Our results might account for increases in apnoea frequency and duration previously observed during NREM sleep following exposure to MIH. Our results also have implications for the use of MIH as a therapeutic modality. Key points: Repeated daily mild intermittent hypoxia has been endorsed as a therapy to promote the recovery of respiratory and limb motor dysfunction.One possible side‐effect of this therapy is an increase in apnoeic event number and duration, which is particularly relevant to participants with motor disorders coupled with an increased incidence of sleep apnoea.In this study, we report that increases in apnoeic event number and duration, following exposure to daily intermittent hypoxia, are the result of an increase in respiratory loop gain and the arousal threshold, in participants with obstructive sleep apnoea.Daily exposure to mild intermittent hypoxia also led to an increase in the ventilatory response to arousal.Accordingly, individuals with motor disorders receiving mild intermittent hypoxia as a therapy should be screened for the presence of sleep apnoea, and if present, administration of intermittent hypoxia during hours of wakefulness should be combined with continuous positive airway pressure treatment during sleep. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
5. Mechanisms of severe acute intermittent hypoxia-induced phrenic long-term facilitation
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Nicole L. Nichols and Gordon S. Mitchell
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Male ,medicine.medical_specialty ,Physiology ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Internal medicine ,medicine ,Animals ,Respiratory system ,Hypoxia ,Protein kinase B ,PI3K/AKT/mTOR pathway ,030304 developmental biology ,Motor Neurons ,0303 health sciences ,Neuronal Plasticity ,business.industry ,Long term facilitation ,General Neuroscience ,Intermittent hypoxia ,Motor neuron ,Spinal cord ,digestive system diseases ,Rats ,Phrenic Nerve ,Disease Models, Animal ,medicine.anatomical_structure ,Acute Disease ,Cardiology ,Breathing ,business ,030217 neurology & neurosurgery ,Signal Transduction ,Research Article - Abstract
Moderate acute intermittent hypoxia (mAIH; 35–55 mmHg Pa(O(2))) elicits phrenic long-term facilitation (pLTF) by a mechanism that requires activation of G(q) protein-coupled serotonin type 2 receptors, MEK/ERK MAP kinase, and NADPH oxidase activity and is constrained by cAMP-PKA signaling. In contrast, severe AIH (sAIH; 25–35 mmHg Pa(O(2))) elicits G(s) protein-coupled adenosine type 2 A receptor-dependent pLTF. Another G(s) protein-coupled receptor, serotonin 7 receptors, elicits phrenic motor facilitation (pMF) by a mechanism that requires exchange protein activated by cyclic AMP (EPAC) and phosphatidylinositol 3-kinase/Akt (PI3K/Akt) activation and is constrained by NADPH oxidase activity. Here, we tested the hypothesis that the same downstream signaling mechanisms giving rise to serotonin 7 (vs. serotonin 2) receptor-induced pMF underlie sAIH-induced pLTF. In anesthetized rats, sAIH-induced pLTF was compared after pretreatment with intrathecal (C4) injections of inhibitors for: 1) EPAC (ESI-05); 2) MEK/ERK (UO126); 3) PKA (KT-5720); 4) PI3K/Akt (PI828); and 5) NADPH oxidase (apocynin). In partial agreement with our hypothesis, sAIH-induced pLTF was abolished by ESI-05 and PI828 and marginally enhanced by apocynin but, surprisingly, was abolished by UO126 and attenuated by KT-5720. Mechanisms of sAIH-induced pLTF reflect elements of both G(q) and G(s) pathways to pMF, likely as a consequence of the complex, cross-talk interactions between them. NEW & NOTEWORTHY Distinct mechanisms give rise to pLTF induced by moderate and severe AIH. We demonstrate that, unlike moderate AIH, severe AIH-induced pLTF requires EPAC and PI3K/Akt and is marginally constrained by NADPH oxidase activity. Surprisingly, sAIH-induced pLTF requires MEK/ERK activity similar to moderate AIH-induced pLTF and is reduced by PKA inhibition. We suggest sAIH-induced pLTF arises from complex interactions between dominant mechanisms characteristic of moderate versus severe AIH-induced pLTF.
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- 2021
6. Shift from short‐term competition to facilitation with drought stress is due to a decrease in long‐term facilitation
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Ghassen Chaieb, Chedly Abdelly, Xiangtai Wang, and Richard Michalet
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Drought stress ,Long term facilitation ,Ecology ,media_common.quotation_subject ,Facilitation ,Biology ,Ecology, Evolution, Behavior and Systematics ,Competition (biology) ,Term (time) ,media_common - Published
- 2020
7. Long-term facilitation of catecholamine secretion from adrenal chromaffin cells of neonatal rats by chronic intermittent hypoxia
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Vladislav V. Makarenko, Ying-Jie Peng, Aaron P. Fox, Jayasri Nanduri, Shakil A. Khan, and Nanduri R. Prabhakar
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medicine.medical_specialty ,Medullary cavity ,Apnea ,Physiology ,Chromaffin Cells ,Infant, Premature, Diseases ,Rats, Sprague-Dawley ,03 medical and health sciences ,Catecholamines ,0302 clinical medicine ,Internal medicine ,Animals ,Medicine ,Chronic intermittent hypoxia ,Secretion ,Hypoxia ,Apnea of prematurity ,030304 developmental biology ,0303 health sciences ,business.industry ,Long term facilitation ,General Neuroscience ,medicine.disease ,Store-operated calcium entry ,Rats ,Disease Models, Animal ,Endocrinology ,Animals, Newborn ,Adrenal Medulla ,Chronic Disease ,Catecholamine ,business ,030217 neurology & neurosurgery ,Research Article ,Adrenal chromaffin ,medicine.drug - Abstract
In neonates, catecholamine (CA) secretion from adrenal medullary chromaffin cells (AMC) is an important mechanism for maintaining homeostasis during hypoxia. Nearly 90% of premature infants experience chronic intermittent hypoxia (IH) because of high incidence of apnea of prematurity, which is characterized by periodic stoppage of breathing. The present study examined the effects of repetitive hypoxia, designed to mimic apnea of prematurity, on CA release from AMC of neonatal rats. Neonatal rats were exposed to either control conditions or chronic intermittent hypoxia (IH) from ages postnatal days 0–5 (P0–P5), and CA release from adrenal medullary slices was measured after challenge with repetitive hypoxia (5 episodes of 30-s hypoxia, Po2~35 mmHg). In response to repetitive hypoxia, chronic IH-treated AMC exhibited sustained CA release, and this phenotype was not seen in control AMC. The sustained CA release was associated with long-lasting elevation of intracellular Ca2+concentration ([Ca2+]i), which was due to store-operated Ca2+entry (SOCE). 2-Aminoethoxydiphenyl borate, an inhibitor of SOCE, prevented the long-lasting [Ca2+]ielevation and CA release. Repetitive hypoxia increased H2O2abundance, and polyethylene glycol (PEG)-catalase, a scavenger of H2O2blocked this effect. PEG-catalase also prevented repetitive hypoxia-induced SOCE activation, sustained [Ca2+]ielevation, and CA release. These results demonstrate that repetitive hypoxia induces long-term facilitation of CA release in chronic IH-treated neonatal rat AMC through sustained Ca2+influx mediated by SOCE.NEW & NOTEWORTHY Apnea of prematurity and the resulting chronic intermittent hypoxia are major clinical problems in neonates born preterm. Catecholamine release from adrenal medullary chromaffin cells maintains homeostasis during hypoxia in neonates. Our results demonstrate that chronic intermittent hypoxia induces a hitherto uncharacterized long-term facilitation of catecholamine secretion from neonatal rat chromaffin cells in response to repetitive hypoxia, simulating hypoxic episodes encountered during apnea of prematurity. The sustained catecholamine secretion might contribute to cardiovascular morbidities in infants with apnea of prematurity.
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- 2019
8. Intermittent hypercapnic hypoxia: a model to study human respiratory motor plasticity?
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Joseph F. Welch
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Male ,Physiology ,Long term facilitation ,business.industry ,Sensory system ,Intermittent hypoxia ,Hypoxia (medical) ,Plasticity ,Hypercapnia ,medicine ,Humans ,Female ,medicine.symptom ,Respiratory system ,Hypoxia ,business ,Neuroscience - Published
- 2021
9. Divergent receptor utilization is necessary for phrenic long-term facilitation over the course of motor neuron loss following CTB-SAP intrapleural injections
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Lauren F. Borkowski, Nicole L. Nichols, Amy N Keilholz, and Catherine L Smith
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Male ,Cholera Toxin ,Receptor, Adenosine A2A ,Physiology ,Long-Term Potentiation ,030204 cardiovascular system & hematology ,complex mixtures ,Rats, Sprague-Dawley ,03 medical and health sciences ,Phosphatidylinositol 3-Kinases ,0302 clinical medicine ,Medicine ,Animals ,Receptor, trkB ,Respiratory system ,Receptor ,Extracellular Signal-Regulated MAP Kinases ,Motor Neurons ,Long term facilitation ,business.industry ,General Neuroscience ,Brain-Derived Neurotrophic Factor ,Respiration ,Motor neuron ,Spinal cord ,Saporins ,Rats ,Phrenic Nerve ,medicine.anatomical_structure ,Receptors, Serotonin ,Synapses ,Facilitation ,Breathing ,business ,Neuroscience ,Proto-Oncogene Proteins c-akt ,030217 neurology & neurosurgery ,Research Article - Abstract
Intrapleural injection of cholera toxin B conjugated to saporin (CTB-SAP) mimics respiratory motor neuron death and respiratory deficits observed in rat models of neuromuscular diseases. Seven-day CTB-SAP rats elicit enhanced phrenic long-term facilitation (pLTF) primarily through TrkB and PI3K/Akt-dependent mechanisms [i.e., Gs-pathway, which can be initiated by adenosine 2A (A2A) receptors in naïve rats], whereas 28-day CTB-SAP rats elicit moderate pLTF though BDNF- and MEK-/ERK-dependent mechanisms [i.e., Gq-pathway, which is typically initiated by serotonin (5-HT) receptors in naïve rats]. Here, we tested the hypothesis that pLTF following CTB-SAP is 1) A2A receptor-dependent at 7 days and 2) 5-HT receptor-dependent at 28 days. Adult Sprague–Dawley male rats were anesthetized, paralyzed, ventilated, and exposed to acute intermittent hypoxia (AIH; 3-, 5-min bouts of 10.5% O(2)) following bilateral, intrapleural injections at 7 days and 28 days of 1) CTB-SAP (25 µg) or 2) unconjugated CTB and SAP (control). Intrathecal C(4) delivery included either the 1) A2A receptor antagonist (MSX-3; 10 µM; 12 µL) or 2) 5-HT receptor antagonist (methysergide; 20 mM; 15 µL). pLTF was abolished with A2A receptor inhibition in 7-day, not 28-day, CTB-SAP rats versus controls (P < 0.05), whereas pLTF was abolished following 5-HT receptor inhibition in 28-day, not 7-day, CTB-SAP rats versus controls (P < 0.05). In addition, 5-HT2A receptor expression was unchanged in CTB-SAP rats versus controls, whereas 5-HT2B receptor expression was decreased in CTB-SAP rats versus controls (P < 0.05). This study furthers our understanding of the contribution of differential receptor activation to pLTF and its implications for breathing following respiratory motor neuron death. NEW & NOTEWORTHY The current study investigates underlying receptor-dependent mechanisms contributing to phrenic long-term facilitation (pLTF) following CTB-SAP-induced respiratory motor neuron death at 7 days and 28 days. We found that A2A receptors are required for enhanced pLTF in 7-day CTB-SAP rats, whereas 5-HT receptors are required for moderate pLTF in 28-day CTB-SAP rats. Targeting these time-dependent mechanisms have implications for breathing maintenance over the course of many neuromuscular diseases.
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- 2021
10. The Influence of Circulating Sex Hormones on Severe Intermittent Hypoxia‐Induced Phrenic Long‐Term Facilitation in Female and Male Rats
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Brendan J. Dougherty
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medicine.medical_specialty ,business.industry ,Long term facilitation ,Intermittent hypoxia ,Biochemistry ,Endocrinology ,Internal medicine ,Male rats ,Genetics ,medicine ,business ,Molecular Biology ,Biotechnology ,Hormone - Published
- 2021
11. Daily administration of ketoprofen restores AIH‐induced phrenic long term facilitation with prolonged chronic intermittent hypoxia
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Mohamad El‐Chami, Gordon S. Mitchell, and Elisa J. Gonzalez-Rothi
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Ketoprofen ,Long term facilitation ,business.industry ,Anesthesia ,Genetics ,medicine ,Chronic intermittent hypoxia ,business ,Molecular Biology ,Biochemistry ,Biotechnology ,medicine.drug - Published
- 2021
12. Acute Intermittent Optogenetic Stimulation of Median Preoptic Nucleus (MnPO) Induces Sympathetic Long‐term Facilitation (sLTF)
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J. Cunningham, Obed Paundralingga, and Caroline Gusson Shimoura
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business.industry ,Long term facilitation ,Genetics ,Medicine ,Stimulation ,Optogenetics ,business ,Molecular Biology ,Biochemistry ,Neuroscience ,Median preoptic nucleus ,Biotechnology - Published
- 2021
13. Cervical spinal 5-HT2A and 5-HT2B receptors are both necessary for moderate acute intermittent hypoxia-induced phrenic long-term facilitation
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Arash Tadjalli and Gordon S. Mitchell
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0301 basic medicine ,MAPK/ERK pathway ,Physiology ,Long term facilitation ,business.industry ,Intermittent hypoxia ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Physiology (medical) ,Facilitation ,Medicine ,Serotonin ,Receptor ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Serotonin (5-HT) is a key regulator of spinal respiratory motor plasticity. For example, spinal 5-HT receptor activation is necessary for the induction of phrenic long-term facilitation (pLTF), a form of respiratory motor plasticity triggered by moderate acute intermittent hypoxia (mAIH). mAIH-induced pLTF is blocked by cervical spinal application of the broad-spectrum 5-HT-receptor antagonist, methysergide. However, methysergide does not allow distinctions between the relative contributions of different 5-HT receptor subtypes. Intravenous administration of the Gq protein-coupled 5-HT2A/2C receptor antagonist ketanserin blocks mAIH-induced pLTF when administered before, but not after, mAIH; thus, 5-HT2 receptor activation is necessary for the induction but not maintenance of mAIH-induced pLTF. However, systemic ketanserin administration does not identify the site of the relevant 5-HT2A/2C receptors. Furthermore, this approach does not differentiate between the roles of 5-HT2A versus 5-HT2C receptors, nor does it preclude involvement of other Gq protein-coupled metabotropic 5-HT receptors capable of eliciting long-lasting phrenic motor facilitation, such as 5-HT2B receptors. Here we tested the hypothesis that mAIH-induced pLTF requires cervical spinal 5-HT2 receptor activation and determined which 5-HT2 receptor subtypes are involved. Anesthetized, paralyzed, and ventilated adult male Sprague Dawley rats were pretreated intrathecally with cervical (~C3-C5) spinal injections of subtype selective 5-HT2A/2C, 5-HT2B, or 5-HT2C receptor antagonists before mAIH. Whereas cervical spinal 5-HT2C receptor inhibition had no impact on mAIH-induced pLTF, pLTF was no longer observed after pretreatment with either 5-HT2A/2C or 5-HT2B receptor antagonists. Furthermore, spinal pretreatment with an MEK/ERK MAPK inhibitor blocked phrenic motor facilitation elicited by intrathecal injections of 5-HT2A but not 5-HT2B receptor agonists. Thus, mAIH-induced pLTF requires concurrent cervical spinal activation of both 5-HT2A and 5-HT2B receptors. However, these distinct receptor subtypes contribute to phrenic motor facilitation via distinct downstream signaling cascades that differ in their requirement for ERK MAPK signaling. The demonstration that both 5-HT2A and 5-HT2B receptors make unique contributions to mAIH-induced pLTF advances our understanding of mechanisms that underlie 5-HT-induced phrenic motor plasticity. NEW & NOTEWORTHY Moderate acute intermittent hypoxia (mAIH) triggers a persistent enhancement in phrenic motor output, an effect termed phrenic long-term facilitation (pLTF). mAIH-induced pLTF is blocked by cervical spinal application of the broad-spectrum serotonin (5-HT) receptor antagonist methysergide, demonstrating the need for spinal 5-HT receptor activation. However, the exact type of 5-HT receptors required for initiation of pLTF remains unknown. To the best of our knowledge, the present study is the first to demonstrate that 1) spinal coactivation of two distinct Gq protein-coupled 5-HT2 receptor subtypes is necessary for mAIH-induced pLTF, and 2) these receptors contribute to pLTF via cascades that differ in their requirement for ERK MAPK signaling.
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- 2019
14. Acute intermittent hypoxia evokes ventilatory long-term facilitation and active expiration in unanesthetized rats
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Bolival A. Mendonça-Junior, Daniel B. Zoccal, Marcos Vinicius Fernandes, and Universidade Estadual Paulista (UNESP)
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Pulmonary and Respiratory Medicine ,Male ,Serotonin ,Plasticity ,Physiology ,Rats, Sprague-Dawley ,immune system diseases ,medicine ,Tidal Volume ,Animals ,Expiration ,Respiratory system ,Hypoxia ,Breathing pattern ,Long term facilitation ,business.industry ,General Neuroscience ,Intermittent hypoxia ,Hypoxia (medical) ,digestive system diseases ,Rats ,Disease Models, Animal ,Anesthesia ,Facilitation ,Respiratory Mechanics ,Serotonin 5-HT2 Receptor Antagonists ,Ketanserin ,medicine.symptom ,business ,Pulmonary Ventilation ,Respiratory minute volume - Abstract
Made available in DSpace on 2022-04-29T08:31:26Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Acute intermittent hypoxia (AIH) modifies the functioning of the respiratory network, causing respiratory motor facilitation in anesthetized animals and a compensatory increase in pulmonary ventilation in freely behaving animals. However, it is still unclear whether the ventilatory facilitation induced by AIH in unanesthetized animals is associated with changes in the respiratory pattern. We found that Holtzman male rats (80–150 g) exposed to AIH (10 × 6% O2 for 30–40 s every 5 min, n = 9) exhibited a prolonged (30 min) increase in baseline minute ventilation (P < 0.05) compared to control animals (n = 13), combined with the occurrence of late expiratory peak flow events, suggesting the presence of active expiration. The increase in ventilation after AIH was also accompanied by reductions in arterial CO2 and body temperature (n = 5–6, P < 0.05). The systemic treatment with ketanserin (a 5-HT2 receptor antagonist) before AIH prevented the changes in ventilation and active expiration (n = 11) but potentiated the hypothermic response (n = 5, P < 0.05) when compared to appropriate control rats (n = 13). Our findings indicate that the ventilatory long-term facilitation elicited by AIH exposure in unanesthetized rats is linked to the generation of active expiration by mechanisms that may depend on the activation of serotonin receptors. In contrast, the decrease in body temperature induced by AIH may not require 5-HT2 receptor activation. Department of Physiology and Pathology School of Dentistry of Araraquara São Paulo State University (UNESP) Department of Physiology and Pathology School of Dentistry of Araraquara São Paulo State University (UNESP) CAPES: 001 CNPq: 132363/2018-6 FAPESP: 2013/17251-6 FAPESP: 2018/21000-2 CNPq: 310331/2017-0 CNPq: 408950/2018-8 CAPES: 88887.194785/2018-00
- Published
- 2021
15. The role of high loop gain induced by intermittent hypoxia in the pathophysiology of obstructive sleep apnoea.
- Author
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Deacon, Naomi L. and Catcheside, Peter G.
- Abstract
Summary Intermittent hypoxia and unstable breathing are key features of obstructive sleep apnoea (OSA), the most common pathological problem of breathing in sleep. Unstable ventilatory control is characterised by high loop gain (LG), and likely contributes to cyclical airway obstruction by promoting airway collapse during periods of low ventilatory drive. Potential new strategies to treat OSA include manipulations designed to lower LG. However, the contribution of inherent versus induced LG abnormalities in OSA remains unclear. Hence, a better understanding of the mechanisms causing high LG in OSA is needed to guide the design of LG based treatments. OSA patients exhibit abnormal chemoreflex control which contributes to increased LG. These abnormalities have been shown to normalise after continuous positive airway pressure treatment, suggesting induced rather than inherent trait abnormalities. Experimental intermittent hypoxia, mimicking OSA, increases hypoxic chemosensitivity and induces long term facilitation; a sustained increase in ventilatory neural output which outlasts the original stimulus. These neuroplastic changes induce the same abnormalities in chemoreflex control as seen in OSA patients. This review outlines the evidence to support that a key component of high LG in OSA is induced by intermittent hypoxia, and is reversed by simply preventing this inducing stimulus. [ABSTRACT FROM AUTHOR]
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- 2015
- Full Text
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16. Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation
- Author
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Megan B Blackburn, Glenn M. Toney, and Mary Ann Andrade
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Male ,Sympathetic Nervous System ,Physiology ,Long-Term Potentiation ,030204 cardiovascular system & hematology ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,immune system diseases ,Physiology (medical) ,medicine ,Biological neural network ,Animals ,Hypoxia ,Long term facilitation ,business.industry ,Respiration ,Sympathetic nerve activity ,Intermittent hypoxia ,digestive system diseases ,Rats ,Phrenic Nerve ,medicine.anatomical_structure ,Blood pressure ,nervous system ,Synaptic plasticity ,Facilitation ,business ,Nucleus ,Neuroscience ,030217 neurology & neurosurgery ,Paraventricular Hypothalamic Nucleus ,Research Article - Abstract
Blackburn MB, Andrade MA, Toney GM. Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation. J Appl Physiol 124: 1233–1243, 2018. First published December 19, 2017; doi: 10.1152/japplphysiol.00743.2017 .— Acute intermittent hypoxia (AIH) repetitively activates the arterial chemoreflex and triggers a progressive increase of sympathetic nerve activity (SNA) and phrenic nerve activity (PNA) referred to as sympathetic and phrenic long-term facilitation (S-LTF and P-LTF), respectively. Neurons of the hypothalamic paraventricular nucleus (PVN) participate in the arterial chemoreflex, but their contribution to AIH-induced LTF is unknown. To determine this, anesthetized rats were vagotomized and exposed to 10 cycles of AIH, each consisting of ventilation for 3 min with 100% O2 followed by 3 min with 15% O2. Before AIH, rats received bilateral PVN injections of artificial cerebrospinal fluid (aCSF; vehicle) or the GABA-A receptor agonist muscimol (100 pmol in 50 nl) to inhibit neuronal activity. Thirty minutes after completing the AIH protocol, during which rats were continuously ventilated with 100% O2, S-LTF and P-LTF were quantified from recordings of integrated splanchnic SNA and PNA, respectively. PVN muscimol attenuated increases of SNA during hypoxic episodes occurring in later cycles (6–10) of AIH ( P < 0.03) and attenuated post-AIH S-LTF ( P < 0.001). Muscimol, however, did not consistently affect peak PNA responses during hypoxic episodes and did not alter AIH-induced P-LTF. These findings indicate that PVN neuronal activity contributes to sympathetic responses during AIH and to subsequent generation of S-LTF. NEW & NOTEWORTHY Neural circuits mediating acute intermittent hypoxia (AIH)-induced sympathetic and phrenic long-term facilitation (LTF) have not been fully elucidated. We found that paraventricular nucleus (PVN) inhibition attenuated sympathetic activation during episodes of AIH and reduced post-AIH sympathetic LTF. Neither phrenic burst patterning nor the magnitude of AIH-induced phrenic LTF was affected. Findings indicate that PVN neurons contribute to AIH-induced sympathetic LTF. Defining mechanisms of sympathetic LTF could improve strategies to reduce sympathetic activity in cardiovascular and metabolic diseases.
- Published
- 2018
17. Chronic Intermittent Hypoxia Induces the Long-Term Facilitation of Genioglossus Corticomotor Activity
- Author
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Xinshi Nie, Ying Zou, Jian Kang, and Wei Wang
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Male ,Pulmonary and Respiratory Medicine ,Article Subject ,medicine.medical_treatment ,Electromyography ,Diseases of the respiratory system ,Random Allocation ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Tongue ,Animals ,Medicine ,Chronic intermittent hypoxia ,030212 general & internal medicine ,Rats, Wistar ,Hypoxia ,Muscle, Skeletal ,Genioglossus ,RC705-779 ,medicine.diagnostic_test ,business.industry ,Long term facilitation ,Hypoxia (medical) ,medicine.disease ,Transcranial Magnetic Stimulation ,Obstructive sleep apnea ,Transcranial magnetic stimulation ,Anesthesia ,Cortical Excitability ,medicine.symptom ,business ,Airway ,030217 neurology & neurosurgery ,Research Article - Abstract
Obstructive sleep apnea (OSA) is characterized by the repetitive collapse of the upper airway and chronic intermittent hypoxia (CIH) during sleep. It has been reported that CIH can increase the EMG activity of genioglossus in rats, which may be related to the neuromuscular compensation of OSA patients. This study aimed to explore whether CIH could induce the long-term facilitation (LTF) of genioglossus corticomotor activity. 16 rats were divided into the air group (n=8) and the CIH group (n=8). The CIH group was exposed to hypoxia for 4 weeks; the air group was subjected to air under identical experimental conditions in parallel. Transcranial magnetic stimulation (TMS) was applied every ten minutes and lasted for 1 h/day on the 1st, 3rd, 7th, 14th, 21st, and 28th days of air/CIH exposure. Genioglossus EMG was also recorded at the same time. Compared with the air group, the CIH group showed decreased TMS latency from 10 to 60 minutes on the 7th, 14th, 21st, and 28th days. The increased TMS amplitude lasting for 60 minutes was only observed on the 21st day. Genioglossus EMG activity increased only on the 28th day of CIH. We concluded that CIH could induce LTF of genioglossus corticomotor activity in rats.
- Published
- 2018
18. Enhancement of phrenic long-term facilitation following repetitive acute intermittent hypoxia is blocked by the glycolytic inhibitor 2-deoxyglucose
- Author
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Stéphane Vinit, Gordon S. Mitchell, and Peter M. MacFarlane
- Subjects
Male ,0301 basic medicine ,Time Factors ,Antimetabolites ,Physiology ,Long-Term Potentiation ,Nitric Oxide Synthase Type II ,Deoxyglucose ,Motor Activity ,Gene Expression Regulation, Enzymologic ,03 medical and health sciences ,0302 clinical medicine ,Physiology (medical) ,Animals ,Medicine ,Glycolysis ,Respiratory system ,Hypoxia ,Phrenic nerve ,business.industry ,Long term facilitation ,Intermittent hypoxia ,Phrenic Nerve ,Disease Models, Animal ,030104 developmental biology ,Rats, Inbred Lew ,Facilitation ,business ,Neuroscience ,030217 neurology & neurosurgery ,Research Article - Abstract
Moderate acute intermittent hypoxia (mAIH) elicits a form of respiratory motor plasticity known as phrenic long-term facilitation (pLTF). Preconditioning with modest protocols of chronic intermittent hypoxia enhances pLTF, demonstrating pLTF metaplasticity. Since “low-dose” protocols of repetitive acute intermittent hypoxia (rAIH) show promise as a therapeutic modality to restore respiratory (and nonrespiratory) motor function in clinical disorders with compromised breathing, we tested 1) whether preconditioning with a mild rAIH protocol enhances pLTF and hypoglossal (XII) LTF and 2) whether the enhancement is regulated by glycolytic flux. In anesthetized, paralyzed, and ventilated adult male Lewis rats, mAIH (three 5-min episodes of 10% O2) elicited pLTF (pLTF at 60 min post-mAIH: 49 ± 5% baseline). rAIH preconditioning (ten 5-min episodes of 11% O2/day with 5-min normoxic intervals, 3 times per week, for 4 wk) significantly enhanced pLTF (100 ± 16% baseline). XII LTF was unaffected by rAIH. When glycolytic flux was inhibited by 2-deoxy-d-glucose (2-DG) administered via drinking water (~80 mg·kg−1·day−1), pLTF returned to normal levels (58 ± 8% baseline); 2-DG had no effect on pLTF in normoxia-pretreated rats (59 ± 7% baseline). In ventral cervical (C4/5) spinal homogenates, rAIH increased inducible nitric oxide synthase mRNA vs. normoxic controls, an effect blocked by 2-DG. However, there were no detectable effects of rAIH or 2-DG on several molecules associated with phrenic motor plasticity, including serotonin 2A, serotonin 7, brain-derived neurotrophic factor, tropomyosin receptor kinase B, or VEGF mRNA. We conclude that modest, but prolonged, rAIH elicits pLTF metaplasticity and that a drug known to inhibit glycolytic flux (2-DG) blocks pLTF enhancement.
- Published
- 2018
19. Serotonin-induced in vitro long-term facilitation exhibits differential pattern sensitivity in cervical and thoracic inspiratory motor output
- Author
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Lovett-Barr, M.R., Mitchell, G.S., Satriotomo, I., and Johnson, S.M.
- Subjects
- *
SPINAL cord , *CENTRAL nervous system , *SEROTONIN , *CEREBROSPINAL fluid - Abstract
Abstract: Intermittent hypoxia induces 5-HT-dependent, pattern-sensitive long-term facilitation (LTF) of spinal respiratory motor output. We used a split-bath in vitro neonatal rat brainstem–spinal cord preparation to test whether: 1) intermittent spinal 5-HT exposure (without hypoxia) is sufficient to induce LTF in phrenic and intercostal inspiratory motor outputs; 2) LTF magnitude is greater in intercostal versus phrenic activity; and 3) phrenic and intercostal motor output exhibits differential pattern sensitivity to 5-HT application. With a barrier at spinal segment C1, 5-HT (5 μM) was applied episodically (3 min 5-HT, 5 min wash, ×3) to the spinal cord (C2–L1) while recording inspiratory bursts in cervical (C4 or C5) and thoracic (T5 or T6) ventral roots. Episodic 5-HT application increased cervical and thoracic burst amplitudes to 136±22% and 150±22% of baseline, respectively, at 120 min post-drug (P<0.01). Continuous 5-HT application (5 μM, 9 min) had no effect on cervical burst amplitude at 120 min post-drug, but increased thoracic burst amplitude to 142±11% of baseline at 120 min post-drug (P<0.001). Methysergide pretreatment abolished both cervical and thoracic 5-HT-induced LTF. Quantitative reverse transcriptase–polymerase chain reaction and immunocytochemistry revealed that 5-HT2A and 5-HT7 receptor subtypes (receptors known to influence LTF expression in adult rats) are expressed in ventral cervical and thoracic spinal cord with no differences in expression levels due to spinal segment or age. Thus, 5-HT is sufficient to induce spinal LTF in neonatal rats and differences in pattern sensitivity suggest heterogeneity in underlying mechanisms. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
20. Long-Term Facilitation Following Acute Intermittent Hypoxia Is Present in People with Cervical Spinal Cord Injury During Non-REM Sleep
- Author
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Sarah Vaughan, Abdulghani Sankari, E. Kruppe, Anan Salloum, S.W. Carroll, and M.S. Badr
- Subjects
business.industry ,Long term facilitation ,Anesthesia ,Cervical spinal cord injury ,Medicine ,Intermittent hypoxia ,business ,Non-rapid eye movement sleep - Published
- 2019
21. Spinal Adenosine 2A Receptor Activation is Necessary for Phrenic Long‐Term Facilitation in Carotid‐Denervated Rats
- Author
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Paul Kubilis, Gordon S. Mitchell, and Raphael R. Perim
- Subjects
medicine.medical_specialty ,Long term facilitation ,business.industry ,Biochemistry ,Adenosine ,Endocrinology ,Internal medicine ,Genetics ,medicine ,business ,Molecular Biology ,Receptor activation ,Biotechnology ,medicine.drug - Published
- 2019
22. An acute exposure to intermittent negative airway pressure elicits respiratory long-term facilitation in awake humans
- Author
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Joshua G Benson, Harry Griffin, Kristian Coomaraswamy, Brendan G Cooper, George M. Balanos, and Shoug Al Humoud
- Subjects
Pulmonary and Respiratory Medicine ,Male ,Time Factors ,Adolescent ,Physiology ,business.industry ,Long term facilitation ,General Neuroscience ,Ventilators, Negative-Pressure ,Stimulus (physiology) ,Hypercapnia ,Young Adult ,INAP ,Control of respiration ,Acute exposure ,Anesthesia ,Facilitation ,Respiratory Mechanics ,Medicine ,Humans ,Respiratory system ,Wakefulness ,Airway ,business ,Pulmonary Ventilation - Abstract
Background A sustained elevation in respiratory drive following removal of the inducing stimulus is known as respiratory long-term facilitation (rLTF). We investigated whether an acute exposure to intermittent negative airway pressure (INAP) elicits rLTF in humans. Method 13 healthy males (20.9 ± 2.8 years) undertook two trials (INAP and Control). In the INAP trial participants were exposed to one hour of 30-second episodes of breathing against negative pressure (-10 cmH2O) interspersed by 60-second intervals of breathing at atmospheric pressure. In the Control trial participants breathed at atmospheric pressure for one hour. Ventilation following INAP (recovery phase) was compared to that during baseline. Results Ventilation increased from baseline to recovery in the INAP trial (14.9 ± 0.9 vs 19.1 ± 0.7 L/min, P = 0.002). This increase was significantly greater than the equivalent during the Control trial (P = 0.019). Data shown as mean ± SEM. Conclusion In this study INAP elicited rLTF in awake, healthy humans. Further research is required to investigate the responsible mechanisms.
- Published
- 2019
23. Spinal Conversion of Testosterone to Estradiol for the Expression of Phrenic Long‐term Facilitation in Adult Male Rats
- Author
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Brendan J. Dougherty, Elena Tyurina, and Danielle McIntosh
- Subjects
medicine.medical_specialty ,Endocrinology ,Adult male ,business.industry ,Long term facilitation ,Internal medicine ,Genetics ,Medicine ,Testosterone (patch) ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2018
24. Blockade of central angiotensin II AT1 receptors attenuates acute intermittent hypoxia‐induced sympathetic long‐term facilitation (S‐LTF)
- Author
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Caroline Gusson Shimoura, Glenn M. Toney, and Mary Ann Andrade
- Subjects
medicine.medical_specialty ,Angiotensin II receptor type 1 ,Long term facilitation ,business.industry ,Intermittent hypoxia ,Biochemistry ,Angiotensin II ,Blockade ,Endocrinology ,Internal medicine ,Genetics ,medicine ,business ,Receptor ,Molecular Biology ,Biotechnology - Published
- 2018
25. Inflammation Differentially Impacts Phrenic Long‐term Facilitation (pLTF) in Rats with Motor Neuron Death Induced by Intrapleural CTB‐saporin Injections
- Author
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Miles A. Tanner and Nicole L. Nichols
- Subjects
0301 basic medicine ,Saporin ,biology ,business.industry ,Long term facilitation ,Inflammation ,Motor neuron ,Biochemistry ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,Genetics ,biology.protein ,Medicine ,medicine.symptom ,business ,Molecular Biology ,Neuroscience ,030217 neurology & neurosurgery ,Biotechnology - Published
- 2018
26. Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea
- Author
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Naomi Deacon-Diaz
- Subjects
medicine.medical_specialty ,Physiology ,business.industry ,Long term facilitation ,Intermittent hypoxia ,medicine.disease ,Sleep in non-human animals ,Arousal ,Obstructive sleep apnea ,Internal medicine ,Cardiology ,Medicine ,business ,Loop gain - Published
- 2019
27. Exposure to mild intermittent hypoxia increases loop gain and the arousal threshold in participants with obstructive sleep apnoea.
- Author
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Deacon‐Diaz, Naomi L.
- Subjects
- *
HYPOXEMIA , *SLEEP , *SLEEP apnea syndromes - Abstract
The article discusses increase in loop gain and the arousal threshold in participants with obstructive sleep apnoea from exposure to mild intermittent hypoxia. Topics include apnoeas followed by arousal and hyperventilation, producing hypocapnia, stability of the ventilatory chemoreflex negative feedback system, and symptom of neurocognitive deficit and fatigue.
- Published
- 2019
- Full Text
- View/download PDF
28. Chronic intermittent hypoxia induces the long-term facilitation of genioglossus corticomotor activity
- Author
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Ying Zou and Wei Wang
- Subjects
Genioglossus ,Long term facilitation ,business.industry ,Anesthesia ,Chronic intermittent hypoxia ,Medicine ,business - Published
- 2017
29. Acute exposure to intermittent negative airway pressure elicits respiratory long-term facilitation in awake humans
- Author
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Shoug Al Humoud, George M. Balanos, Brendan G Cooper, Harry Griffin, and Josh Benson
- Subjects
Recovery period ,INAP ,Long term facilitation ,business.industry ,Control of respiration ,Anesthesia ,Acute exposure ,Medicine ,Intermittent hypoxia ,Respiratory system ,business ,Airway - Abstract
A sustained elevation in respiratory drive following removal of a stimulus is known as respiratory long-term facilitation (rLTF). This phenomenon has been well demonstrated in humans and other animals following intermittent hypoxia. Potential clinical benefits of enhancing respiratory drive with intermittent hypoxia are likely to be offset by its side effects. However, intermittent negative airway pressure (INAP) has recently been shown in rats to elicit a similar magnitude of rLTF as IH but could have fewer side effects. We investigated whether INAP elicits rLTF in awake humans. 13 healthy male volunteers (20.9 ± 2.8 years) undertook two trials (INAP and Control). In the INAP trial, participants were exposed to one hour of 30-second episodes of negative pressure (-10 cmH 2 O) interspersed by 60-second intervals of atmospheric pressure. In the Control trial, participants breathed at atmospheric pressure for one hour. Changes in ventilation were assessed by comparing ventilation during the final five minutes of a 20-minute baseline period, with the final five minutes of a one-hour recovery period. In the Control trial ventilation increased from 14.7 ± 0.8 L/min during baseline to 16.9 ± 0.9 L/min in recovery (P=0.023). However, in the INAP trial ventilation increased significantly more (P=0.019) between baseline and recovery (14.9 ± 0.9 vs 19.1 ± 0.7 L/min, P=0.002). Data shown as mean ± SEM. In this study INAP elicits rLTF in awake, healthy humans. Further research is required to investigate the responsible mechanisms and determine if this form of rLTF could benefit patients with respiratory insufficiency.
- Published
- 2017
30. Episode Frequency Determines the Impact of Chronic Intermittent Hypoxia on Phrenic Long Term Facilitation
- Author
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Raphael R. Perim, Arash Tadjalli, Gordon S Mitchell, Marissa C. Ciesla, Alec K Simon, and Elisa Janine Gonzalez‐Rothi
- Subjects
medicine.medical_specialty ,business.industry ,Long term facilitation ,Internal medicine ,Genetics ,Cardiology ,medicine ,Chronic intermittent hypoxia ,business ,Molecular Biology ,Biochemistry ,Biotechnology - Published
- 2017
31. Synaptic Tagging and Capture ☆
- Author
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Diego Moncada
- Subjects
medicine.anatomical_structure ,Long-term memory ,Long term facilitation ,Aplysia ,Synaptic plasticity ,medicine ,Long-term potentiation ,Neuron ,Biology ,Long-term depression ,biology.organism_classification ,Neuroscience ,Synaptic tagging - Abstract
The requirement for transcription during long-lasting forms of learning-related synaptic plasticity raises the question of how the products of gene expression can be targeted to alter synaptic strength at some, but not all, synapses made by a neuron. The synaptic tagging hypothesis proposes that the products of gene expression are delivered throughout the cell, but they only function to increase synaptic strength when they are ‘captured’ at specific synapses that have been ‘tagged’ by previous synaptic activity. Studies in a variety of systems have confirmed the existence of synaptic tagging and capture and its analog at learning and memory level, the Behavioral tagging. Current research is aimed at identifying the molecular nature of the tag and the processes that modulate the tagging and capture process.
- Published
- 2017
32. Author response: Transient inhibition and long-term facilitation of locomotion by phasic optogenetic activation of serotonin neurons
- Author
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Zachary F. Mainen, Patrícia A. Correia, Dhruba Banerjee, Eran Lottem, Ana S Machado, and Megan R. Carey
- Subjects
Long term facilitation ,Chemistry ,Transient (computer programming) ,Serotonin ,Optogenetics ,Neuroscience - Published
- 2016
33. Intermittent hypercapnic hypoxia during sleep does not induce ventilatory long-term facilitation in healthy males
- Author
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Daniel Stadler, Peter Catcheside, Doug R. McEvoy, and Naomi Deacon
- Subjects
Male ,Time Factors ,Physiology ,Polysomnography ,030204 cardiovascular system & hematology ,Arousal ,Hypercapnia ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Physiology (medical) ,Neuroplasticity ,medicine ,Humans ,Hypoxia ,Neuronal Plasticity ,business.industry ,Long term facilitation ,Electromyography ,Sleep apnea ,Intermittent hypoxia ,Hypoxia (medical) ,medicine.disease ,Chemoreceptor Cells ,Anesthesia ,Concomitant ,medicine.symptom ,business ,Pulmonary Ventilation ,Sleep ,030217 neurology & neurosurgery - Abstract
Intermittent hypoxia-induced ventilatory neuroplasticity is likely important in obstructive sleep apnea pathophysiology. Although concomitant CO2levels and arousal state critically influence neuroplastic effects of intermittent hypoxia, no studies have investigated intermittent hypercapnic hypoxia effects during sleep in humans. Thus the purpose of this study was to investigate if intermittent hypercapnic hypoxia during sleep induces neuroplasticity (ventilatory long-term facilitation and increased chemoreflex responsiveness) in humans. Twelve healthy males were exposed to intermittent hypercapnic hypoxia (24 × 30 s episodes of 3% CO2and 3.0 ± 0.2% O2) and intermittent medical air during sleep after 2 wk washout period in a randomized crossover study design. Minute ventilation, end-tidal CO2, O2saturation, breath timing, upper airway resistance, and genioglossal and diaphragm electromyograms were examined during 10 min of stable stage 2 sleep preceding gas exposure, during gas and intervening room air periods, and throughout 1 h of room air recovery. There were no significant differences between conditions across time to indicate long-term facilitation of ventilation, genioglossal or diaphragm electromyogram activity, and no change in ventilatory response from the first to last gas exposure to suggest any change in chemoreflex responsiveness. These findings contrast with previous intermittent hypoxia studies without intermittent hypercapnia and suggest that the more relevant gas disturbance stimulus of concomitant intermittent hypercapnia frequently occurring in sleep apnea influences acute neuroplastic effects of intermittent hypoxia. These findings highlight the need for further studies of intermittent hypercapnic hypoxia during sleep to clarify the role of ventilatory neuroplasticity in the pathophysiology of sleep apnea.NEW & NOTEWORTHY Both arousal state and concomitant CO2levels are known modulators of the effects of intermittent hypoxia on ventilatory neuroplasticity. This is the first study to investigate the effects of combined intermittent hypercapnic hypoxia during sleep in humans. The lack of neuroplastic effects suggests a need for further studies more closely replicating obstructive sleep apnea to determine the pathophysiological relevance of intermittent hypoxia-induced ventilatory neuroplasticity.
- Published
- 2016
34. Recurrent laryngeal nerve activity exhibits a 5-HT-mediated long-term facilitation and enhanced response to hypoxia following acute intermittent hypoxia in rat
- Author
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Paul M. Pilowsky, Tao Xing, Tara G. Bautista, and Angelina Y. Fong
- Subjects
Male ,Serotonin ,Physiology ,Methysergide ,Blood Pressure ,Rats, Sprague-Dawley ,Physiology (medical) ,Recurrent laryngeal nerve ,medicine ,Animals ,Hypoxia, Brain ,5-HT receptor ,Recurrent Laryngeal Nerve ,Long term facilitation ,business.industry ,Laryngeal Nerves ,Intermittent hypoxia ,Hypoxia (medical) ,Electric Stimulation ,Electrophysiological Phenomena ,Rats ,Phrenic Nerve ,Data Interpretation, Statistical ,Anesthesia ,Facilitation ,Serotonin Antagonists ,Blood Gas Analysis ,Laryngeal Muscles ,medicine.symptom ,business ,medicine.drug - Abstract
A progressive and sustained increase in inspiratory-related motor output (“long-term facilitation”) and an augmented ventilatory response to hypoxia occur following acute intermittent hypoxia (AIH). To date, acute plasticity in respiratory motor outputs active in the postinspiratory and expiratory phases has not been studied. The recurrent laryngeal nerve (RLN) innervates laryngeal abductor muscles that widen the glottic aperture during inspiration. Other efferent fibers in the RLN innervate adductor muscles that partially narrow the glottic aperture during postinspiration. The aim of this study was to investigate whether or not AIH elicits a serotonin-mediated long-term facilitation of laryngeal abductor muscles, and if recruitment of adductor muscle activity occurs following AIH. Urethane anesthetized, paralyzed, unilaterally vagotomized, and artificially ventilated adult male Sprague-Dawley rats were subjected to 10 exposures of hypoxia (10% O2 in N2, 45 s, separated by 5 min, n = 7). At 60 min post-AIH, phrenic nerve activity and inspiratory RLN activity were elevated (39 ± 11 and 23 ± 6% above baseline, respectively). These responses were abolished by pretreatment with the serotonin-receptor antagonist, methysergide ( n = 4). No increase occurred in time control animals ( n = 7). Animals that did not exhibit postinspiratory RLN activity at baseline did not show recruitment of this activity post-AIH ( n = 6). A repeat hypoxia 60 min after AIH produced a significantly greater peak response in both phrenic and RLN activity, accompanied by a prolonged recovery time that was also prevented by pretreatment with methysergide. We conclude that AIH induces neural plasticity in laryngeal motoneurons, via serotonin-mediated mechanisms similar to that observed in phrenic motoneurons: the so-called “Q-pathway”. We also provide evidence that the augmented responsiveness to repeat hypoxia following AIH also involves a serotonergic mechanism.
- Published
- 2012
35. Similarities and differences in mechanisms of phrenic and hypoglossal motor facilitation
- Author
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Tracy L. Baker-Herman and Kristi A. Strey
- Subjects
Motor Neurons ,Pulmonary and Respiratory Medicine ,Hypoglossal Nerve ,Physiology ,Long term facilitation ,General Neuroscience ,Intermittent hypoxia ,Article ,Phrenic Nerve ,Neural activity ,Control of respiration ,Respiratory Mechanics ,Facilitation ,Animals ,Humans ,HLTF ,Psychology ,Hypoglossal nerve ,Neuroscience ,Phrenic nerve - Abstract
Intermittent hypoxia-induced long-term facilitation (LTF) is variably expressed in the motor output of several inspiratory nerves, such as the phrenic and hypoglossal. Compared to phrenic LTF (pLTF), less is known about hypoglossal LTF (hLTF), although it is often assumed that cellular mechanisms are the same. While fundamental mechanisms appear to be similar, potentially important differences exist in the modulation of pLTF and hLTF. The primary objectives of this paper are to: (1) review similarities and differences in pLTF and hLTF, pointing out knowledge gaps and (2) present new data suggesting that reduced respiratory neural activity elicits differential plasticity in phrenic and hypoglossal output (inactivity-induced phrenic and hypoglossal motor facilitation, iPMF and iHMF), suggesting that these motor pool-specific differences are not unique to LTF. Differences in fundamental mechanisms or modulation of plasticity among motor pools may confer the capacity to mount a complex ventilatory response to specific challenges, particularly in motor pools with different “jobs” in the control of breathing.
- Published
- 2011
36. Should we standardize protocols and preparations used to study respiratory plasticity?
- Author
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Gordon S. Mitchell and Jiro Terada
- Subjects
Pulmonary and Respiratory Medicine ,Physiology ,Long term facilitation ,Mechanism (biology) ,General Neuroscience ,Intermittent hypoxia ,Respiratory system ,Plasticity ,Biology ,Neuroscience - Published
- 2011
37. Propofol abolished the phrenic long-term facilitation in rats
- Author
-
Nenad Karanović, Renata Pecotić, Mladen Carev, Zoran Dogas, Zoran Valic, Ivana Pavlinac, and Maja Valić
- Subjects
Male ,Pulmonary and Respiratory Medicine ,Time Factors ,respiration ,phrenic nerve ,intermittent hypoxia ,propofol ,rats ,neuronal plasticity ,Physiology ,Long-Term Potentiation ,Burst frequency ,Action Potentials ,Vagotomy ,Urethane ,Rats, Sprague-Dawley ,medicine ,Animals ,Hypnotics and Sedatives ,Hypoxia ,Propofol ,Urethane anesthesia ,Phrenic nerve ,Baseline values ,Analysis of Variance ,business.industry ,Long term facilitation ,Respiration ,General Neuroscience ,Intermittent hypoxia ,Hypoxia (medical) ,Respiration, Artificial ,Electric Stimulation ,Rats ,Electrophysiology ,Phrenic Nerve ,Anesthesia ,Tracheotomy ,medicine.symptom ,business ,medicine.drug - Abstract
The aim was to investigate the effect of propofol anesthesia on the phrenic long-term facilitation (LTF) in rats. We hypothesized that there would be a significant attenuation of LTF during propofol compared with urethane anesthesia. Fourteen adult, male, anesthetized, vagotomized, paralyzed, and mechanically ventilated Sprague-Dawley rats (7 per group), were exposed to the acute intermittent hypoxia (AIH) protocol. Peak phrenic nerve amplitude (PNA), burst frequency (f), and breathing rhythm parameters (Ti, Te, Ttot) were analyzed during the first hypoxia (TH1), as well as at 15 (T15), 30 (T30), and 60 minutes (T60) after the final hypoxic episode, and compared to the baseline values. In propofol-anesthetized rats no significant changes of PNA were recorded after the last hypoxic episode, i.e. no LTF was induced. There was a significant increase of PNA (59.4 ± 6.6%, p
- Published
- 2010
38. Inspiratory activation is not required for episodic hypoxia-induced respiratory long-term facilitation in postnatal rats
- Author
-
Arash Tadjalli, James Duffin, John H. Peever, Hyunwook Hong, and Yan Mei Li
- Subjects
medicine.medical_specialty ,Physiology ,Long term facilitation ,Hypoxia (medical) ,Biology ,Stimulus (physiology) ,Endocrinology ,Internal medicine ,Anesthesia ,Time course ,Facilitation ,medicine ,Brainstem ,Respiratory system ,medicine.symptom ,Phrenic nerve - Abstract
Episodic hypoxia causes repetitive inspiratory activation that induces a form of respiratory plasticity termed long-term facilitation (LTF). While LTF is a function of the hypoxic exposures and inspiratory activation, their relative importance in evoking LTF is unknown. The aims of this study were to: (1) dissociate the relative roles played by episodic hypoxia and respiratory activation in LTF; and (2) determine whether the magnitude of LTF varies as a function of hypoxic intensity. We did this by examining the effects of episodic hypoxia in postnatal rats (15–25 days old), which unlike adult rats exhibit a prominent hypoxia-induced respiratory depression. We quantified inspiratory phrenic nerve activity generated by the in situ working-heart brainstem before, during and for 60 min after episodic hypoxia. We demonstrate that episodic hypoxia evokes LTF despite the fact that it potently suppresses inspiratory activity during individual hypoxic exposures (P 0.05). To determine if LTF magnitude was affected by hypoxic intensity, the episodic hypoxia protocol was repeated under three different O2 tensions. We demonstrate that the magnitude and time course of LTF depend on hypoxic severity, with more intense hypoxia inducing a more potent degree of LTF. We conclude that inspiratory activation is not required for LTF induction, and that hypoxia per se is the physiological stimulus for eliciting hypoxia-induced respiratory LTF.
- Published
- 2007
39. Increased Ca2+influx through Na+/Ca2+exchanger during long-term facilitation at crayfish neuromuscular junctions
- Author
-
Akira Minami, Yan‐fang Xia, and Robert S. Zucker
- Subjects
Physiology ,Long term facilitation ,Ca2 influx ,Transporter ,Biology ,Neurotransmission ,Motor neuron ,Crayfish ,medicine.anatomical_structure ,Reverse mode ,medicine ,Biophysics ,Facilitation ,Neuroscience - Abstract
Intense motor neuron activity induces a long-term facilitation (LTF) of synaptic transmission at crayfish neuromuscular junctions (NMJs) that is accompanied by an increase in the accumulation of presynaptic Ca2+ ions during a test train of action potentials. It is natural to assume that the increased Ca2+ influx during action potentials is directly responsible for the increased transmitter release in LTF, especially as the magnitudes of LTF and increased Ca2+ influx are positively correlated. However, our results indicate that the elevated Ca2+ entry occurs through the reverse mode operation of presynaptic Na+/Ca2+ exchangers that are activated by an LTF-inducing tetanus. Inhibition of Na+/Ca2+ exchange blocks this additional Ca2+ influx without affecting LTF, showing that LTF is not a consequence of the regulation of these transporters and is not directly related to the increase in [Ca2+]i reached during a train of action potentials. Their correlation is probably due to both being induced independently by the strong [Ca2+]i elevation accompanying LTF-inducing stimuli. Our results reveal a new form of regulation of neuronal Na+/Ca2+ exchange that does not directly alter the strength of synaptic transmission.
- Published
- 2007
40. Phrenic motor neuron TrkB expression is necessary for acute intermittent hypoxia-induced phrenic long-term facilitation
- Author
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Erica A. Dale, Michael J. Devinney, Daryl P. Fields, and Gordon S. Mitchell
- Subjects
0301 basic medicine ,Male ,Cholera Toxin ,Time Factors ,Long-Term Potentiation ,Down-Regulation ,Tropomyosin receptor kinase B ,Vagotomy ,Transfection ,Article ,Rats, Sprague-Dawley ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,Adjuvants, Immunologic ,Medicine ,Animals ,Receptor, trkB ,Respiratory system ,RNA, Small Interfering ,Receptor ,Hypoxia ,Brain-derived neurotrophic factor ,Motor Neurons ,business.industry ,Long term facilitation ,musculoskeletal, neural, and ocular physiology ,Intermittent hypoxia ,Motor neuron ,Carbon Dioxide ,musculoskeletal system ,Rats ,Phrenic Nerve ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,nervous system ,Facilitation ,business ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Phrenic long-term facilitation (pLTF) is a form of hypoxia-induced spinal respiratory motor plasticity that requires new synthesis of brain derived neurotrophic factor (BDNF) and activation of its high-affinity receptor, tropomyosin receptor kinase B (TrkB). Since the cellular location of relevant TrkB receptors is not known, we utilized intrapleural siRNA injections to selectively knock down TrkB receptor protein within phrenic motor neurons. TrkB receptors within phrenic motor neurons are necessary for BDNF-dependent acute intermittent hypoxia-induced pLTF, demonstrating that phrenic motor neurons are a critical site of respiratory motor plasticity.
- Published
- 2015
41. Mammalian target of rapamycin is required for phrenic long-term facilitation following severe but not moderate acute intermittent hypoxia
- Author
-
Daryl P. Fields, Brendan J. Dougherty, and Gordon S. Mitchell
- Subjects
Male ,Adenosine ,Physiology ,Control of Homeostasis ,Long-Term Potentiation ,Mechanistic Target of Rapamycin Complex 1 ,Rats, Sprague-Dawley ,Medicine ,Animals ,Hypoxia ,PI3K/AKT/mTOR pathway ,Phrenic nerve ,business.industry ,Long term facilitation ,General Neuroscience ,TOR Serine-Threonine Kinases ,Intermittent hypoxia ,Hypoxia (medical) ,Motor neuron ,Rats ,Phrenic Nerve ,medicine.anatomical_structure ,Multiprotein Complexes ,Facilitation ,medicine.symptom ,business ,Neuroscience - Abstract
Phrenic long-term facilitation (pLTF) is a persistent increase in phrenic nerve activity after acute intermittent hypoxia (AIH). Distinct cell-signaling cascades give rise to pLTF depending on the severity of hypoxemia within hypoxic episodes. Moderate AIH (mAIH; three 5-min episodes, PaO2 ∼35–55 mmHG) elicits pLTF by a serotonin (5-HT)-dependent mechanism that requires new synthesis of brain-derived neurotrophic factor (BDNF), activation of its high-affinity receptor (TrkB), and ERK MAPK signaling. In contrast, severe AIH (sAIH; three 5-min episodes, PaO2 ∼25–30 mmHG) elicits pLTF by an adenosine-dependent mechanism that requires new TrkB synthesis and Akt signaling. Although both mechanisms require spinal protein synthesis, the newly synthesized proteins are distinct, as are the neurochemicals inducing plasticity (serotonin vs. adenosine). In many forms of neuroplasticity, new protein synthesis requires translational regulation via mammalian target of rapamycin (mTOR) signaling. Since Akt regulates mTOR activity, we hypothesized that mTOR activity is necessary for sAIH- but not mAIH-induced pLTF. Phrenic nerve activity in anesthetized, paralyzed, and ventilated rats was recorded before, during, and 60 min after mAIH or sAIH. Rats were pretreated with intrathecal injections of 20% DMSO (vehicle controls) or rapamycin (0.1 mM, 12 μl), a selective mTOR complex 1 inhibitor. Consistent with our hypothesis, rapamycin blocked sAIH- but not mAIH-induced pLTF. Thus spinal mTOR activity is required for adenosine-dependent (sAIH) but not serotonin-dependent (mAIH) pLTF, suggesting that distinct mechanisms regulate new protein synthesis in these forms of spinal neuroplasticity.
- Published
- 2015
42. Hypoglossal long term facilitation shifts the power spectral density to higher frequencies
- Author
-
Mai K. ElMallah, David D. Fuller, and David A Stanley
- Subjects
Physics ,Nuclear magnetic resonance ,Long term facilitation ,Genetics ,Spectral density ,Molecular Biology ,Biochemistry ,Biotechnology ,Coherence (physics) - Abstract
The frequency content of electrical activity in respiratory nerves shows distinct bands of increased content (power). Above approximately 75 Hz these bands show coherence across different respirato...
- Published
- 2015
43. Phrenic Long‐term Facilitation (pLTF) Following Acute Intermittent Hypoxia is NADPH Oxidase Independent in a Rat Model (SOD1 G93A ) of ALS
- Author
-
Nicole L. Nichols and Gordon S. Mitchell
- Subjects
NADPH oxidase ,biology ,business.industry ,Long term facilitation ,Rat model ,Intermittent hypoxia ,Pharmacology ,Biochemistry ,Anesthesia ,Genetics ,biology.protein ,Medicine ,business ,Molecular Biology ,Biotechnology - Published
- 2015
44. HIF‐2α Deficiency Induces Carotid Body Sensory Long‐Term Facilitation
- Author
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Nanduri R. Prabhakar, Ning Wang, Shakil A. Khan, Ying-Jie Peng, Jayasri Nanduri, and Gregg L. Semenza
- Subjects
medicine.anatomical_structure ,business.industry ,Long term facilitation ,Genetics ,medicine ,Carotid body ,Sensory system ,business ,Molecular Biology ,Biochemistry ,Neuroscience ,Biotechnology - Published
- 2015
45. Differential Roles of Mammalian Target of Rapamycin (mTOR) in Phrenic Long‐Term Facilitation
- Author
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Daryl P. Fields, Gordon S. Mitchell, and Brendan J. Dougherty
- Subjects
Long term facilitation ,RPTOR ,Genetics ,Biology ,Molecular Biology ,Biochemistry ,Neuroscience ,PI3K/AKT/mTOR pathway ,Differential (mathematics) ,Biotechnology - Published
- 2015
46. Serotoninergic Antagonism in the Retrotrapezoid Nucleus Prevents the Expiratory Long‐Term Facilitation Induced by Acute Intermittent Hypoxia
- Author
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Daniel B. Zoccal, Eduardo V. Lemes, and Eduardo Colombari
- Subjects
business.industry ,Long term facilitation ,Genetics ,Medicine ,Intermittent hypoxia ,Retrotrapezoid nucleus ,business ,Antagonism ,Serotonergic ,Molecular Biology ,Biochemistry ,Neuroscience ,Biotechnology - Published
- 2015
47. Pontine A7 and A5 noradrenergic neuronal groups mediate long‐term facilitation of hypoglossal motor activity induced by episodic airway obstruction
- Author
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Gang Song and Chi-Sang Poon
- Subjects
medicine.medical_specialty ,Long term facilitation ,business.industry ,Airway obstruction ,medicine.disease ,Biochemistry ,Sleep in non-human animals ,Airway occlusion ,respiratory tract diseases ,Obstructive sleep apnea ,stomatognathic system ,Internal medicine ,Genetics ,Cardiology ,Medicine ,Genioglossus muscle ,Motor activity ,business ,Molecular Biology ,Biotechnology - Abstract
In obstructive sleep apnea (OSA), decreased noradrenergic activation of genioglossus muscle during REM sleep results in repetitive upper airway occlusion, a neurodegenerative process that aggravate...
- Published
- 2015
48. Role of serotonergic 5-HT1A receptors in phrenic long term facilitation elicited by acute intermittent hypoxia in rats
- Author
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Pavlinac Dodig, Ivana
- Subjects
nervous system ,musculoskeletal, neural, and ocular physiology ,polycyclic compounds ,heterocyclic compounds ,Long term facilitation ,Phrenic ,Rat - Abstract
The aims were to investigate the role of 5-HT1A receptor activation in induction and preservation of phrenic long term facilitation (pLTF) at two different time points, before exposures to acute intermittent hypoxia (AIH) and after pLTF was induced and to examine the effects of 5-HT1A receptors blockade by selective antagonist WAY- 100635 into the caudal raphe region on pLTF elicited by AIH. We found that 5-HT1A receptor activation plays a significant role in both induction and preservation of pLTF. Furthermore, activation of the 5-HT1A receptors at supraspinal level is important for induction of pLTF.
- Published
- 2015
49. Episodic hypoxia induces long-term facilitation of neural drive to tongue protrudor and retractor muscles
- Author
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David D. Fuller
- Subjects
Male ,Hypoglossal Nerve ,Physiology ,Tongue ,Physiology (medical) ,Animals ,Medicine ,Hypoxia, Brain ,business.industry ,Long term facilitation ,Hypoxia (medical) ,Respiratory Muscles ,Rats ,Phrenic Nerve ,Retractor ,medicine.anatomical_structure ,Inhalation ,Rats, Inbred Lew ,Anesthesia ,Facilitation ,Respiratory control ,Neuron ,Blood Gas Analysis ,medicine.symptom ,business - Abstract
Hypoxic episodes can evoke a prolonged augmentation of inspiratory motor output called long-term facilitation (LTF). Hypoglossal (XII) LTF has been assumed to represent increased tongue protrudor muscle activation and pharyngeal airway dilation. However, recent studies indicate that tongue protrudor and retractor muscles are coactivated during inspiration, a behavior that promotes upper airway patency by reducing airway compliance. These experiments tested the hypothesis that XII LTF is manifest as increased inspiratory drive to both tongue protrudor and retractor muscles. Neurograms were recorded in the medial XII nerve branch (XIIMED; contains tongue protrudor motor axons), the lateral XII nerve branch (XIILAT; contains tongue retractor motor axons), and the phrenic nerve in anesthetized, vagotomized, paralyzed, ventilated male rats. Strict isocapnia was maintained for 60 min after five 3-min hypoxic episodes (arterial Po2 = 35 ± 2 Torr) or sham treatment. Peak inspiratory burst amplitude showed a persistent increase in XIIMED, XIILAT, and phrenic nerves during the hour after episodic hypoxia ( P < 0.05 vs. sham). This effect was present regardless of the quantification method (e.g., % baseline vs. percent maximum); however, comparisons of the relative magnitude of LTF between neurograms (e.g., XIIMED vs. XIILAT) varied with the normalization procedure. There was no persistent effect of episodic hypoxia on inspiratory burst frequency ( P > 0.05 vs. sham). These data demonstrate that episodic hypoxia induces LTF of inspiratory drive to both tongue protrudor and retractor muscles and underscore the potential contribution of tongue muscle coactivation to regulation of upper airway patency.
- Published
- 2005
50. Ventilatory long-term facilitation is greater in 1- vs. 2-mo-old awake rats
- Author
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Michelle McGuire and Liming Ling
- Subjects
Male ,Aging ,Time Factors ,Adult male ,Physiology ,Rats, Sprague-Dawley ,Oxygen Consumption ,Physiology (medical) ,Respiration ,Animals ,Medicine ,Chronic intermittent hypoxia ,Wakefulness ,Respiratory system ,Hypoxia ,business.industry ,Long term facilitation ,Hypoxia (medical) ,Adaptation, Physiological ,Rats ,Oxygen ,Anesthesia ,Facilitation ,medicine.symptom ,Pulmonary Ventilation ,business - Abstract
Respiratory long-term facilitation (LTF) declines in middle-aged vs. adult male rats. Chronic intermittent hypoxia (CIH; 5 min 11–12% O2/5 min air, 12 h/night, 7 nights) enhances LTF in adult rats. However, LTF in immature rats and the effect of early CIH are unevaluated. The present study compared LTF in 1- and 2-mo-old rats and examined the effect of neonatal CIH (initiated at 2 days after birth) on the LTF. Ventilatory LTF, elicited by 5 ( protocol 1) or 10 ( protocol 2) episodes of poikilocapnic hypoxia (5 min 12% O2/5 min air), was measured twice by plethysmography on the same male conscious rat when it was 1 and 2 mo old. In untreated (without CIH) rats, both resting ventilation (54.7 ± 0.6 vs. 43.0 ± 0.2 ml·100 g−1·min−1) and hypoxic ventilatory response (131 ± 4 vs. 66 ± 3% above baseline) were greater in 1- vs. 2-mo-old rats. Protocol 1 elicited LTF in 1-mo-old (12.5 ± 1.0% above baseline) but not 2-mo-old rats. Protocol 2 elicited a greater LTF in 1-mo-old (24.3 ± 0.8%) vs. 2-mo-old rats (18.2 ± 0.5%). In CIH-treated rats, protocol 1 also elicited LTF in 1-mo-old (13.1 ± 1.5%) but not 2-mo-old rats. Protocol 2 elicited LTF in both age groups, but LTF was enhanced by the CIH only in 1-mo-old rats (28.8 ± 0.9%). These results suggest that ventilatory LTF and hypoxic ventilatory response are greater in male rats shortly before their sexual maturity and that the neonatal CIH somewhat enhances ventilatory LTF ∼3 wk after CIH, but this enhancement does not last to adulthood.
- Published
- 2005
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