Evidence map›Paper›PMID 31159922›Full record

ArticleeLife2019

Dissociating orexin-dependent and -independent functions of orexin neurons using novel Orexin-Flp knock-in mice.

Srikanta Chowdhury, Chi Jung Hung, Shuntaro Izawa, Ayumu Inutsuka, Meiko Kawamura, Takashi Kawashima, Haruhiko Bito, Itaru Imayoshi, Manabu Abe, Kenji Sakimura and 1 more

Open access · goldAbstract read
In one paragraph

Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

19 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
  2. Article
  3. Neurotensin in the extended amygdala maintains wakefulness in novel environments.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  5. Review
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  8. Deficiency of orexin signaling during sleep is involved in abnormal REM sleep architecture in narcolepsy.Proceedings of the National Academy of Sciences of the United States of America · 2023
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  9. Article
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  11. STAR protocols · 2022
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  12. Article
  13. The hypothalamic link between arousal and sleep homeostasis in mice.Proceedings of the National Academy of Sciences of the United States of America · 2021
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  14. 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

11 authors at 5 institutions in 2 countries.

Srikanta ChowdhuryDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.ORCID 0000-0002-2216-5960
Chi Jung HungDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.ORCID 0000-0002-1169-7953
Shuntaro IzawaDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
Ayumu InutsukaDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.ORCID 0000-0001-6503-5501
Meiko KawamuraDepartment of Animal Model development, Brain Research Institute, Niigata University, Niigata, Japan.
Takashi KawashimaDepartment of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Haruhiko BitoDepartment of Neurochemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Itaru ImayoshiResearch Center for Dynamic Living Systems, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
Manabu AbeDepartment of Animal Model development, Brain Research Institute, Niigata University, Niigata, Japan.
Kenji SakimuraDepartment of Animal Model development, Brain Research Institute, Niigata University, Niigata, Japan.
Akihiro YamanakaDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.ORCID 0000-0001-6099-7306
Japan Science and Technology Agency · JPNiigata University · JPThe University of Tokyo · JPKyoto University · JPNagoya University · JP

Funding

Japan Science and Technology Agency JPMJCR1656Ministry of Education, Culture, Sports, Science and Technology 15H01428Ministry of Education, Culture, Sports, Science and Technology 16H01271Ministry of Education, Culture, Sports, Science and Technology 18KK0223Ministry of Education, Culture, Sports, Science and Technology 19H05016Ministry of Education, Culture, Sports, Science and Technology 26640041Ministry of Education, Culture, Sports, Science, and Technology 26293046
6 · The paper itself

Abstract

Uninterrupted arousal is important for survival during threatening situations. Activation of orexin/hypocretin neurons is implicated in sustained arousal. However, orexin neurons produce and release orexin as well as several co-transmitters including dynorphin and glutamate. To disambiguate orexin-dependent and -independent physiological functions of orexin neurons, we generated a novel Orexin-flippase (Flp) knock-in mouse line. Crossing with Flp-reporter or Cre-expressing mice showed gene expression exclusively in orexin neurons. Histological studies confirmed that orexin was knock-out in homozygous mice. Orexin neurons without orexin showed altered electrophysiological properties, as well as received decreased glutamatergic inputs. Selective chemogenetic activation revealed that both orexin and co-transmitters functioned to increase wakefulness, however, orexin was indispensable to promote sustained arousal. Surprisingly, such activation increased the total time spent in cataplexy. Taken together, orexin is essential to maintain basic membrane properties and input-output computation of orexin neurons, as well as to exert awake-sustaining aptitude of orexin neurons.

Indexed as

ArousalWakefulnessAction PotentialsAnimalsBehavior, AnimalMiceNeuronsOrexinsOrexinscataplexychemogeneticselectrophysiologyflippase recombinasemouseneuroscienceorexin/hypocretinsleep/wakefulness

Identifiers

PMID31159922
PMCPMC6548533
OpenAlexW2949510726

What OpenQuestion holds

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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.