Evidence map›Paper›PMID 26096172›Full record

ArticleThe European journal of neuroscience2015

The retrotrapezoid nucleus stimulates breathing by releasing glutamate in adult conscious mice.

Benjamin B Holloway, Kenneth E Viar, Ruth L Stornetta, Patrice G Guyenet

Open access · greenAbstract read
In one paragraph

Article in The European journal of neuroscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.2field-weighted citation impact, top 14% 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

26 citing papers in PubMed, 37 citations in OpenAlex.

  1. Article
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  3. Respiratory Depression Associated with Opioids: A Narrative Review.Current treatment options in oncology · 2024
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  9. Central respiratory chemoreception.Handbook of clinical neurology · 2022
    Review
  10. Adolescent Congenital Central Hypoventilation Syndrome: An Easily Overlooked Diagnosis.International journal of environmental research and public health · 2021
    Review
  11. Chemoreceptor mechanisms regulating COThe Journal of physiology · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. Review
  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

4 authors at 1 institution in 1 country.

Benjamin B HollowayDepartment of Pharmacology, University of Virginia Health System, P.O. Box 800735, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0735, USA.
Kenneth E ViarDepartment of Pharmacology, University of Virginia Health System, P.O. Box 800735, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0735, USA.
Ruth L StornettaDepartment of Pharmacology, University of Virginia Health System, P.O. Box 800735, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0735, USA.
Patrice G GuyenetDepartment of Pharmacology, University of Virginia Health System, P.O. Box 800735, 1340 Jefferson Park Avenue, Charlottesville, VA, 22908-0735, USA.
University of Virginia Health System · US

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 HL028785NHLBI NIH HHS HL 074011NHLBI NIH HHS R01 HL028785NHLBI NIH HHS R01 HL074011NHLBI NIH HHS R37 HL028785
6 · The paper itself

Abstract

The retrotrapezoid nucleus (RTN) is a bilateral cluster of neurons located at the ventral surface of the brainstem below the facial nucleus. The RTN is activated by hypercapnia and stabilises arterial Pco2 by adjusting lung ventilation in a feedback manner. RTN neurons contain vesicular glutamate transporter-2 (Vglut2) transcripts (Slc17a6), and their synaptic boutons are Vglut2-immunoreactive. Here, we used optogenetics to test whether the RTN increases ventilation in conscious adult mice by releasing glutamate. Neurons located below the facial motor nucleus were transduced unilaterally to express channelrhodopsin-2 (ChR2)-enhanced yellow fluorescent protein, with lentiviral vectors that employ the Phox2b-activated artificial promoter PRSx8. The targeted population consisted of two types of Phox2b-expressing neuron: non-catecholaminergic neurons (putative RTN chemoreceptors) and catecholaminergic (C1) neurons. Opto-activation of a mix of ChR2-expressing RTN and C1 neurons produced a powerful stimulus frequency-dependent (5-15 Hz) stimulation of breathing in control conscious mice. Respiratory stimulation was comparable in mice in which dopamine-β-hydroxylase (DβH)-positive neurons no longer expressed Vglut2 (DβH(C) (re/0);;Vglut2(fl/fl)). In a third group of mice, i.e. DβH(+/+);;Vglut2(fl/fl) mice, we injected a mixture of PRSx8-Cre lentiviral vector and Cre-dependent ChR2 adeno-associated virus 2 unilaterally into the RTN; this procedure deleted Vglut2 from ChR2-expressing neurons regardless of whether or not they were catecholaminergic. The ventilatory response elicited by photostimulation of ChR2-positive neurons was almost completely absent in these mice. Resting ventilatory parameters were identical in the three groups of mice, and their brains contained similar numbers of ChR2-positive catecholaminergic and non-catecholaminergic neurons. From these results, we conclude that RTN neurons increase breathing in conscious adult mice by releasing glutamate.

Indexed as

RespirationAnimalsCatecholaminesChemoreceptor CellsFemaleGlutamic AcidMaleMedulla OblongataMiceMice, Inbred C57BLMice, TransgenicNeuronsOptogeneticsVesicular Glutamate Transport Protein 2CatecholaminesGlutamic AcidSlc17a6 protein, mouseVesicular Glutamate Transport Protein 2breathingcentral respiratory chemoreceptorsglutamateoptogenetics

Identifiers

PMID26096172
PMCPMC4578988
OpenAlexW1512828689

What OpenQuestion holds

Textmetadata
LicenceTDM
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.