ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2014
When norepinephrine becomes a driver of breathing irregularities: how intermittent hypoxia fundamentally alters the modulatory response of the respiratory network.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 63 citations in OpenAlex.
- Noradrenergic neuromodulation produces a NMDAR-dependent network state of respiratory rhythmogenesis in the preBötzinger Complex.bioRxiv : the preprint server for biology · 2026Article
- Divergent ventilatory responses during opioid-induced respiratory depression in response to repeated fentanyl use.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Chronic sustained hypoxia alters the pattern of diaphragm electrical activity in anaesthetized rats.Experimental physiology · 2025Article
- Pharmacological modulation of respiratory control: Ampakines as a therapeutic strategy.Pharmacology & therapeutics · 2025Review
- Review
- Acute effects of the 4-4-8 breathing technique on arterial stiffness in healthy young men.Cardiology journal · 2024Article
- Purinergic signaling mediates neuroglial interactions to modulate sighs.Nature communications · 2023Article
- Arginine vasopressin potentiates inspiratory bursting in hypoglossal motoneurons of neonatal mice.Respiratory physiology & neurobiology · 2023Article
- Fiber optical imaging of astroglial calcium signaling in the respiratory network in the working heart brainstem preparation.Frontiers in physiology · 2023Article
- Mediation of Sinusoidal Network Oscillations in the Locus Coeruleus of Newborn Rat Slices by Pharmacologically Distinct AMPA and KA Receptors.Brain sciences · 2022Article
- Autonomic dysfunction in epilepsy mouse models with implications for SUDEP research.Frontiers in neurology · 2022Review
- Physiological and neurochemical adaptations following abrupt termination of chronic hypercapnia in goats.Journal of applied physiology (Bethesda, Md. : 1985) · 2021Article
- Respiratory rhythm generation, hypoxia, and oxidative stress-Implications for development.Respiratory physiology & neurobiology · 2019Review
- Brainstem network disruption: A pathway to sudden unexplained death in epilepsy?Human brain mapping · 2018Article
- Chronic intermittent hypoxia disrupts cardiorespiratory homeostasis and gut microbiota composition in adult male guinea-pigs.EBioMedicine · 2018Article
- Defining the Rhythmogenic Elements of Mammalian Breathing.Physiology (Bethesda, Md.) · 2018Review
- The Dynamic Basis of Respiratory Rhythm Generation: One Breath at a Time.Annual review of neuroscience · 2018Review
- Effects on breathing of agonists to μ-opioid or GABARespiratory physiology & neurobiology · 2017Article
- Chronic Intermittent Hypoxia Differentially Impacts Different States of Inspiratory Activity at the Level of the preBötzinger Complex.Frontiers in physiology · 2017Article
- Oxidative stress augments chemoreflex sensitivity in rats exposed to chronic intermittent hypoxia.Respiratory physiology & neurobiology · 2016Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
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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Registered trials
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