Evidence map›Paper›PMID 25268747›Full record

ArticlePLoS biology2014

Differentially timed extracellular signals synchronize pacemaker neuron clocks.

Ben Collins, Harris S Kaplan, Matthieu Cavey, Katherine R Lelito, Andrew H Bahle, Zhonghua Zhu, Ann Marie Macara, Gregg Roman, Orie T Shafer, Justin Blau

Abstract read
In one paragraph

Article in PLoS biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
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

32 citing papers in PubMed.

  1. Article
  2. Article
  3. A functional clock in only two dorsal clock neurons is sufficient to restore the basal circadian activity pattern ofProceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Dorsal clock neurons iniScience · 2021
    Article
  10. Article
  11. Article
  12. Entrainment of theNeuroscience insights · 2020
    Review
  13. Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. SIK3-HDAC4 signaling regulatesProceedings of the National Academy of Sciences of the United States of America · 2017
    Article
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

10 authors.

Ben CollinsDepartment of Biology, New York University, New York, New York, United States of America.
Harris S KaplanDepartment of Biology, New York University, New York, New York, United States of America.
Matthieu CaveyDepartment of Biology, New York University, New York, New York, United States of America.
Katherine R LelitoDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
Andrew H BahleDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
Zhonghua ZhuDepartment of Biology, New York University, New York, New York, United States of America.
Ann Marie MacaraDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
Gregg RomanDepartment of Biology and Biochemistry, University of Houston, Houston, Texas, United States of America.
Orie T ShaferDepartment of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, United States of America.
Justin BlauDepartment of Biology, New York University, New York, New York, United States of America; Center for Genomics & Systems Biology, New York University Abu Dhabi Institute, Abu Dhabi, United Arab Emirates; Program in Biology, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates.

Funding

Regulation of pacemaker neuronsR01GM063911 · NIGMS · NEW YORK UNIVERSITY · PI BLAU, JUSTIN · 2002 to 2019
$5.6M
Network Properties of Circadian Clock Modulation and EntrainmentR01NS077933 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI ORIE T SHAFER · 2012 to 2026
$4.9M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR015518 · NCRR · NEW YORK UNIVERSITY · PI LENNIE, PETER · 2000 to 2000
$1.3M
Circuitry and Modulation of the Circardian Clock Network of D. melanogasterR00NS062953 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SHAFER, ORIE T · 2010 to 2012
$732k
Identification of Alcohol Binding Site(s) in Protein Kinase C EpsilonR21AA016140 · NIAAA · UNIVERSITY OF HOUSTON · PI DAS, JOYDIP · 2006 to 2007
$453k
NCRR NIH HHS C06 RR015518NCRR NIH HHS C06 RR-15518-01NIAAA NIH HHS AA016140NIAAA NIH HHS R21 AA016140NIGMS NIH HHS GM063911NIGMS NIH HHS R01 GM063911NINDS NIH HHS R00 NS062953NINDS NIH HHS R00NS62953NINDS NIH HHS R01 NS077933NINDS NIH HHS R01NS077933
6 · The paper itself

Abstract

Synchronized neuronal activity is vital for complex processes like behavior. Circadian pacemaker neurons offer an unusual opportunity to study synchrony as their molecular clocks oscillate in phase over an extended timeframe (24 h). To identify where, when, and how synchronizing signals are perceived, we first studied the minimal clock neural circuit in Drosophila larvae, manipulating either the four master pacemaker neurons (LNvs) or two dorsal clock neurons (DN1s). Unexpectedly, we found that the PDF Receptor (PdfR) is required in both LNvs and DN1s to maintain synchronized LNv clocks. We also found that glutamate is a second synchronizing signal that is released from DN1s and perceived in LNvs via the metabotropic glutamate receptor (mGluRA). Because simultaneously reducing Pdfr and mGluRA expression in LNvs severely dampened Timeless clock protein oscillations, we conclude that the master pacemaker LNvs require extracellular signals to function normally. These two synchronizing signals are released at opposite times of day and drive cAMP oscillations in LNvs. Finally we found that PdfR and mGluRA also help synchronize Timeless oscillations in adult s-LNvs. We propose that differentially timed signals that drive cAMP oscillations and synchronize pacemaker neurons in circadian neural circuits will be conserved across species.

Indexed as

AnimalsCircadian ClocksCircadian RhythmCyclic AMPDrosophila melanogasterDrosophila ProteinsGene Expression RegulationGlutamic AcidLarvaNeuronsNeuropeptidesPhotoperiodReceptors, G-Protein-CoupledReceptors, Metabotropic GlutamateSignal TransductionCyclic AMPDrosophila ProteinsGlutamic AcidmGluR protein, DrosophilaNeuropeptidespdf protein, DrosophilaPDFR protein, DrosophilaReceptors, G-Protein-CoupledReceptors, Metabotropic Glutamatetim protein, Drosophila

Identifiers

PMID25268747
PMCPMC4181961

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.