Evidence map›Paper›PMID 24651580›Full record

ArticlePloS one2014

A physiologically based model of orexinergic stabilization of sleep and wake.

Ben D Fulcher, Andrew J K Phillips, Svetlana Postnova, Peter A Robinson

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.7field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 46 citations in OpenAlex.

  1. Trial
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  3. Article
  4. Article
  5. Disrupted nighttime sleep and sleep instability in narcolepsy.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2022
    Review
  6. Review
  7. Article
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  9. Article
  10. Article
  11. Review
  12. Neuroendocrine Control of Sleep.Current topics in behavioral neurosciences · 2019
    Review
  13. Article
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  15. Article
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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 2 institutions in 2 countries.

Ben D FulcherSchool of Physics, The University of Sydney, Sydney, New South Wales, Australia.
Andrew J K PhillipsDivision of Sleep Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.
Svetlana PostnovaSchool of Physics, The University of Sydney, Sydney, New South Wales, Australia; Center for Integrated Research and Understanding of Sleep, The University of Sydney, Sydney, New South Wales, Australia; Brain Dynamics Center, The University of Sydney, Sydney, New South Wales, Australia.
Peter A RobinsonSchool of Physics, The University of Sydney, Sydney, New South Wales, Australia; Center for Integrated Research and Understanding of Sleep, The University of Sydney, Sydney, New South Wales, Australia; Brain Dynamics Center, The University of Sydney, Sydney, New South Wales, Australia; Cooperative Research Center for Alertness, Safety and Productivity, The University of Sydney, Sydney, New South Wales, Australia.
University of Sydney · AUBrigham and Women's Hospital · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The orexinergic neurons of the lateral hypothalamus (Orx) are essential for regulating sleep-wake dynamics, and their loss causes narcolepsy, a disorder characterized by severe instability of sleep and wake states. However, the mechanisms through which Orx stabilize sleep and wake are not well understood. In this work, an explanation of the stabilizing effects of Orx is presented using a quantitative model of important physiological connections between Orx and the sleep-wake switch. In addition to Orx and the sleep-wake switch, which is composed of mutually inhibitory wake-active monoaminergic neurons in brainstem and hypothalamus (MA) and the sleep-active ventrolateral preoptic neurons of the hypothalamus (VLPO), the model also includes the circadian and homeostatic sleep drives. It is shown that Orx stabilizes prolonged waking episodes via its excitatory input to MA and by relaying a circadian input to MA, thus sustaining MA firing activity during the circadian day. During sleep, both Orx and MA are inhibited by the VLPO, and the subsequent reduction in Orx input to the MA indirectly stabilizes sustained sleep episodes. Simulating a loss of Orx, the model produces dynamics resembling narcolepsy, including frequent transitions between states, reduced waking arousal levels, and a normal daily amount of total sleep. The model predicts a change in sleep timing with differences in orexin levels, with higher orexin levels delaying the normal sleep episode, suggesting that individual differences in Orx signaling may contribute to chronotype. Dynamics resembling sleep inertia also emerge from the model as a gradual sleep-to-wake transition on a timescale that varies with that of Orx dynamics. The quantitative, physiologically based model developed in this work thus provides a new explanation of how Orx stabilizes prolonged episodes of sleep and wake, and makes a range of experimentally testable predictions, including a role for Orx in chronotype and sleep inertia.

Indexed as

Models, BiologicalAnimalsBrain StemComputer SimulationHumansHypothalamusIntracellular Signaling Peptides and ProteinsNarcolepsyNeuronsNeuropeptidesOrexinsPhenotypePreoptic AreaSleepWakefulnessIntracellular Signaling Peptides and ProteinsNeuropeptidesOrexins

Identifiers

PMID24651580
PMCPMC3961294
OpenAlexW2106700773

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.