ArticleAmerican journal of respiratory and critical care medicine2014
Optogenetic stimulation of adrenergic C1 neurons causes sleep state-dependent cardiorespiratory stimulation and arousal with sighs in rats.
Article in American journal of respiratory and critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 96 citations in OpenAlex.
- Molecular changes in hypoxia-induced central neural circuits and nuclei.Medical gas research · 2026Review
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- Astrocyte activation in the ventrolateral medulla modulates breathing and arousal states.Nature communications · 2026Article
- Wavelength-dependent sleep state manipulation using light pulses in Pogona vitticeps.Communications biology · 2026Article
- RVLM C1 Neurons Innervate Sacral as well as Thoracolumbar Autonomic Preganglionic Neurons in the Rat.The Journal of comparative neurology · 2026Article
- Parvalbumin-expressing neurons in the ventral medulla are active during wakefulness and promote NREM sleep.Sleep · 2025Article
- Adrenergic C1 neurons enhance anxiety via projections to PAG.bioRxiv : the preprint server for biology · 2024Article
- Genetic identification of medullary neurons underlying congenital hypoventilation.Science advances · 2024Article
- Fasting-activated ventrolateral medulla neurons regulate T cell homing and suppress autoimmune disease in mice.Nature neuroscience · 2024Article
- Hindbrain Adrenergic/Noradrenergic Control of Integrated Endocrine and Autonomic Stress Responses.Endocrinology · 2023Review
- Article
- AMPK facilitates the hypoxic ventilatory response through non-adrenergic mechanisms at the brainstem.Pflugers Archiv : European journal of physiology · 2023Article
- Descending pathways from the superior colliculus mediating autonomic and respiratory effects associated with orienting behaviour.The Journal of physiology · 2022Article
- Article
- Activity of pontine A7 noradrenergic neurons is suppressed during REM sleep.Journal of applied physiology (Bethesda, Md. : 1985) · 2022Article
- The psychophysiology of the sigh: I: The sigh from the physiological perspective.Biological psychology · 2022Review
- Central regulation of body fluid homeostasis.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2022Review
- Optical Activation of the Dorsal Horn of the Thoracic Spinal Cord Prevents Ventricular Arrhythmias in Acute Myocardial Ischemia-Reperfusion Rats.Frontiers in cardiovascular medicine · 2022Article
- The sigh and related behaviors.Handbook of clinical neurology · 2022Review
- Loss of putative GABAergic neurons in the ventrolateral medulla in multiple system atrophy.Sleep · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
rationaleThe rostral ventrolateral medulla (RVLM) contains central respiratory chemoreceptors (retrotrapezoid nucleus, RTN) and the sympathoexcitatory, hypoxia-responsive C1 neurons. Simultaneous optogenetic stimulation of these neurons produces vigorous cardiorespiratory stimulation, sighing, and arousal from non-REM sleep.
objectivesTo identify the effects that result from selectively stimulating C1 cells.
methodsA Cre-dependent vector expressing channelrhodopsin 2 (ChR2) fused with enhanced yellow fluorescent protein or mCherry was injected into the RVLM of tyrosine hydroxylase (TH)-Cre rats. The response of ChR2-transduced neurons to light was examined in anesthetized rats. ChR2-transduced C1 neurons were photoactivated in conscious rats while EEG, neck muscle EMG, blood pressure (BP), and breathing were recorded. MEASUREMENTS AND MAIN
resultsMost ChR2-expressing neurons (95%) contained C1 neuron markers and innervated the spinal cord. RTN neurons were not transduced. While the rats were under anesthesia, the C1 cells were faithfully activated by each light pulse up to 40 Hz. During quiet resting and non-REM sleep, C1 cell stimulation (20 s, 2-20 Hz) increased BP and respiratory frequency and produced sighs and arousal from non-REM sleep. Arousal was frequency-dependent (85% probability at 20 Hz). Stimulation during REM sleep increased BP, but had no effect on EEG or breathing. C1 cell-mediated breathing stimulation was occluded by hypoxia (12% FIO2), but was unchanged by 6% FiCO2.
conclusionsC1 cell stimulation reproduces most effects of acute hypoxia, specifically cardiorespiratory stimulation, sighs, and arousal. C1 cell activation likely contributes to the sleep disruption and adverse autonomic consequences of sleep apnea. During hypoxia (awake) or REM sleep, C1 cell stimulation increases BP but no longer stimulates breathing.
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