No evidence for long-term facilitation after episodic hypoxia in spontaneously breathing, anesthetized rats

Janssen, P. L.; Fregosi, Ralph F.

doi:10.1152/jappl.2000.89.4.1345

Cited by 44 publications

(46 citation statements)

References 17 publications

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“…7 A, C). AIH alone caused no significant change in the inspiratory frequency confirming that long-term facilitation is not expressed in anesthetized vagus-intact preparations (Janssen and Fregosi, 2000). However, NE injection into the preBötC area followed by exposure to AIH (n ϭ 8) had drastic effects on breathing in vivo (Fig.…”

Section: Aih Alters the Response Of The Respiratory Network To Exogenmentioning

confidence: 61%

When Norepinephrine Becomes a Driver of Breathing Irregularities: How Intermittent Hypoxia Fundamentally Alters the Modulatory Response of the Respiratory Network

et al. 2013

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Neuronal networks are endogenously modulated by aminergic and peptidergic substances. These modulatory processes are critical for maintaining normal activity and adapting networks to changes in metabolic, behavioral, and environmental conditions. However, disturbances in neuromodulation have also been associated with pathologies. Using whole animals (in vivo) and functional brainstem slices (in vitro) from mice, we demonstrate that exposure to acute intermittent hypoxia (AIH) leads to fundamental changes in the neuromodulatory response of the respiratory network located within the preBötzinger complex (preBötC), an area critical for breathing. Norepinephrine, which normally regularizes respiratory activity, renders respiratory activity irregular after AIH. Respiratory irregularities are caused both in vitro and in vivo by AIH, which increases synaptic inhibition within the preBötC when norepinephrine is endogenously or exogenously increased. These irregularities are prevented by blocking synaptic inhibition before AIH. However, regular breathing cannot be reestablished if synaptic inhibition is blocked after AIH. We conclude that subtle changes in synaptic transmission can have dramatic consequences at the network level as endogenously released neuromodulators that are normally adaptive become the drivers of irregularity. Moreover, irregularities in the preBötC result in irregularities in the motor output in vivo and in incomplete transmission of inspiratory activity to the hypoglossus motor nucleus. Our finding has basic science implications for understanding network functions in general, and it may be clinically relevant for understanding pathological disturbances associated with hypoxic episodes such as those associated with myocardial infarcts, obstructive sleep apneas, apneas of prematurity, Rett syndrome, and sudden infant death syndrome.

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Section: Aih Alters the Response Of The Respiratory Network To Exogenmentioning

confidence: 61%

When Norepinephrine Becomes a Driver of Breathing Irregularities: How Intermittent Hypoxia Fundamentally Alters the Modulatory Response of the Respiratory Network

et al. 2013

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“…The small animal size and experimental approach designed to study animals under a number of protocols, precluded blood gas sampling in these studies. In spontaneously breathing rats, 3.0 to 3.5% CO 2 added to a hypoxic gas mixture maintained arterial CO 2 at control levels (20). In addition tidal volumes (Table 1) and lung volumes in Mecp2 ϩ/Ϫ animals were significantly larger than wild type (Fig.…”

Section: Discussionmentioning

confidence: 85%

Separate Respiratory Phenotypes in Methyl-CpG-Binding Protein 2 (Mecp2) Deficient Mice

Bissonnette

Knopp

2006

Pediatr Res

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Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutations in the X-linked gene methyl-CpG-binding protein 2 (MECP2) that encodes a DNA binding protein involved in gene silencing. Selective deletion of Mecp2 in post-mitotic neurons in mice results in a Rett-like phenotype characterized by disturbances in motor activity and body weight, suggesting that these symptoms are exclusively caused by neuronal deficiency. Included in the RTT phenotype are episodes of respiratory depression that follow hyperventilation. Here we show that the respiratory phenotype depends on the organ distribution of Mecp2 deficiency. Both female mice heterozygous for a null mutation in Mecp2 (Mecp2 ϩ/Ϫ ) and those with selective deletion of the protein in neurons (Mecp2 ϩ/nestin-Cre lox ), showed an initial response to hypoxia that exceeded that in wild type (WT). However, marked respiratory depression following hypoxic hyperventilation was only seen in Mecp2 ϩ/Ϫ animals. Addition of carbon dioxide to the hypoxic exposure eliminated the respiratory depression. Tidal volume and lung volume were larger in Mecp2 ϩ/Ϫ and respiratory depression was directly related to tidal volume. Taken together these results indicate that the depression is due to hypocapnia. Respiratory depression in this mouse model of Rett Syndrome is seen in with ubiquitous deficiency in Mecp2 but not when it is confined to neurons. (Pediatr Res 59: 513-518, 2006)

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“…The occurrence and expression of LTF varies across species, CNS arousal state, experimental paradigms and medullary motor nuclei. Episodic hypoxia elicits LTF in many (Maltais et al 1991;Cao et al 1992;Hayashi et al 1993;Mateika and Fregosi, 1997;Turner and Mitchell, 1997;Fregosi and Mitchell, 2000), but not all animal models (Janssen and Fregosi, 2000). Likewise, episodic hypoxia did not elicit LTF during wakefulness in humans (McEvoy et al 1996, Jordan et al 2002, Morris and Gozal.…”

Section: Introductionmentioning

confidence: 98%

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

Chowdhuri

Pierchala

Aboubakr

et al. 2008

Respiratory Physiology & Neurobiology

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Episodic hypoxia (EH) is followed by increased ventilatory motor output in the recovery period indicative of long-term facilitation (LTF). We hypothesized that episodic hypoxia evokes LTF of genioglossus (GG) muscle activity in humans during non-rapid eye movement sleep (NREM) sleep. We studied 12 normal non-flow limited humans during stable NREM sleep. We induced 10 brief (3 minute) episodes of isocapnic hypoxia followed by 5 minutes of room air. Measurements were obtained during control, hypoxia, and at 5, 10, 20, 30 and 40 minutes of recovery, respectively, for minute ventilation (V̇I), supraglottic pressure (P SG ), upper airway resistance (R UA ) and phasic GG electromyogram (EMG GG ). In addition, sham studies were conducted on room air. During hypoxia there was a significant increase in phasic EMG GG (202.7±24.1% of control, p<0.01) and in V̇I (123.0 ±3.3% of control, p<0.05); however, only phasic EMG GG demonstrated a significant persistent increase throughout recovery (198.9±30.9%, 203.6±29.9% and 205.4±26.4% of control, at 5, 10, and 20 minutes of recovery, respectively, p<0.01). In multivariate regression analysis, age and phasic EMG GG activity during hypoxia were significant predictors of EMG GG at recovery 20 minutes. No significant changes in any of the measured parameters were noted during sham studies. Conclusion: 1) EH elicits LTF of GG in normal non-flow limited humans during NREM sleep, without ventilatory or mechanical LTF. 2) GG activity during the recovery period correlates with the magnitude of GG activation during hypoxia, and inversely with age.

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No evidence for long-term facilitation after episodic hypoxia in spontaneously breathing, anesthetized rats

Cited by 44 publications

References 17 publications

When Norepinephrine Becomes a Driver of Breathing Irregularities: How Intermittent Hypoxia Fundamentally Alters the Modulatory Response of the Respiratory Network

When Norepinephrine Becomes a Driver of Breathing Irregularities: How Intermittent Hypoxia Fundamentally Alters the Modulatory Response of the Respiratory Network

Separate Respiratory Phenotypes in Methyl-CpG-Binding Protein 2 (Mecp2) Deficient Mice

Long-term facilitation of genioglossus activity is present in normal humans during NREM sleep

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