Evidence map›Paper›PMID 25858492›Full record

ArticleJournal of applied physiology (Bethesda, Md. : 1985)2015

Selective optogenetic stimulation of the retrotrapezoid nucleus in sleeping rats activates breathing without changing blood pressure or causing arousal or sighs.

Peter G R Burke, Roy Kanbar, Kenneth E Viar, Ruth L Stornetta, Patrice G Guyenet

Abstract read
In one paragraph

Article in Journal of applied physiology (Bethesda, Md. : 1985), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.7field-weighted citation impact, top 18% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 38 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Chemogenetic activation of noradrenergic A5 neurons increases blood pressure and visceral sympathetic activity in adult rats.American journal of physiology. Regulatory, integrative and comparative physiology · 2022
    Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. The sigh and related behaviors.Handbook of clinical neurology · 2022
    Review
  10. Central respiratory chemoreception.Handbook of clinical neurology · 2022
    Review
  11. Chemoreceptor mechanisms regulating COThe Journal of physiology · 2021
    Review
  12. COInterface focus · 2021
    Review
  13. Differential Contribution of the Retrotrapezoid Nucleus and C1 Neurons to Active Expiration and Arousal in Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020
    Article
  14. Connexin26 mediates COCommunications biology · 2020
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 2 countries.

Peter G R BurkeDepartment of Pharmacology, University of Virginia, Charlottesville, Virginia; and.
Roy KanbarDepartment of Pharmaceutical Sciences, Lebanese American University, Beyrouth, Lebanon.
Kenneth E ViarDepartment of Pharmacology, University of Virginia, Charlottesville, Virginia; and.
Ruth L StornettaDepartment of Pharmacology, University of Virginia, Charlottesville, Virginia; and.
Patrice G GuyenetDepartment of Pharmacology, University of Virginia, Charlottesville, Virginia; and pgg@virginia.edu.
University of Virginia · USLebanese American University · LB

Funding

Retrotrapezoid nucleus and central chemoreceptionR01HL074011 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUYENET, PATRICE G. · 2003 to 2018
$6.6M
Organization of Central Sympathic PathwaysR01HL028785 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI STORNETTA, RUTH L · 1985 to 2020
$5.0M
ORGANIZATION OF CENTRAL SYMPATHETIC PATHWAYSR37HL028785 · NHLBI · UNIVERSITY OF VIRGINIA CHARLOTTESVILLE · PI GUYENET, PATRICE G. · 1999 to 2008
$3.0M
NHLBI NIH HHS HL28785NHLBI NIH HHS HL74011NHLBI NIH HHS R01 HL074011
6 · The paper itself

Abstract

Combined optogenetic activation of the retrotrapezoid nucleus (RTN; a CO2/proton-activated brainstem nucleus) with nearby catecholaminergic neurons (C1 and A5), or selective C1 neuron stimulation, increases blood pressure (BP) and breathing, causes arousal from non-rapid eye movement (non-REM) sleep, and triggers sighs. Here we wished to determine which of these physiological responses are elicited when RTN neurons are selectively activated. The left rostral RTN and nearby A5 neurons were transduced with channelrhodopsin-2 (ChR2(+)) using a lentiviral vector. Very few C1 cells were transduced. BP, breathing, EEG, and neck EMG were monitored. During non-REM sleep, photostimulation of ChR2(+) neurons (20s, 2-20 Hz) instantly increased V̇e without changing BP (13 rats). V̇e and BP were unaffected by light in nine control (ChR2(-)) rats. Photostimulation produced no sighs and caused arousal (EEG desynchronization) more frequently in ChR2(+) than ChR2(-) rats (62 ± 5% of trials vs. 25 ± 2%; P < 0.0001). Six ChR2(+) rats then received spinal injections of a saporin-based toxin that spared RTN neurons but destroyed surrounding catecholaminergic neurons. Photostimulation of the ChR2(+) neurons produced the same ventilatory stimulation before and after lesion, but arousal was no longer elicited. Overall (all ChR2(+) rats combined), ΔV̇e correlated with the number of ChR2(+) RTN neurons whereas arousal probability correlated with the number of ChR2(+) catecholaminergic neurons. In conclusion, RTN neurons activate breathing powerfully and, unlike the C1 cells, have minimal effects on BP and have a weak arousal capability at best. A5 neuron stimulation produces little effect on breathing and BP but does appear to facilitate arousal.

Indexed as

RespirationAnimalsArousalBlood PressureCatecholaminesChannelrhodopsinsElectroencephalographyElectroencephalography Phase SynchronizationElectromyographyMaleMuscle, SkeletalOptogeneticsPhotic StimulationRatsRats, Sprague-DawleyRibosome Inactivating Proteins, Type 1CatecholaminesChannelrhodopsinsRibosome Inactivating Proteins, Type 1SaporinsA5 noradrenergic neuronsarousalhypercapnianon-REM sleepretrotrapezoid nucleus

Identifiers

PMID25858492
PMCPMC4469924
OpenAlexW2035475307

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.