Evidence map›Paper›PMID 39694033›Full record

ArticleNeuron2025

Ketamine induces plasticity in a norepinephrine-astroglial circuit to promote behavioral perseverance.

Marc Duque, Alex B Chen, Eric Hsu, Sujatha Narayan, Altyn Rymbek, Shahinoor Begum, Gesine Saher, Adam E Cohen, David E Olson, Yulong Li and 5 more

Abstract read
In one paragraph

Article in Neuron, 2025. 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
–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

17 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Striatal cholinergic and dopaminergic driven astrocyte CabioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. HumanFrontiers in neuroscience · 2025
    Article
  16. Review
  17. 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

15 authors.

Marc DuqueDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Graduate Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: mduqueramirez@g.harvard.edu.
Alex B ChenDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA; Graduate Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA; Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: abchen@g.harvard.edu.
Eric HsuSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Sujatha NarayanJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA.
Altyn RymbekTianqiao and Chrissy Chen Institute for Neuroscience, Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Shahinoor BegumDepartment of Physics, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Gesine SaherDepartment of Neurogenetics, Max Planck Institute for Multidisciplinary Sciences, Göttingen 37075, Germany.
Adam E CohenDepartment of Physics, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
David E OlsonDepartment of Chemistry, University of California, Davis, Davis, CA 95616, USA; Department of Biochemistry & Molecular Medicine, School of Medicine, University of California, Davis, Sacramento, CA 95817, USA; Center for Neuroscience, University of California, Davis, Davis, CA 95618, USA; Institute for Psychedelics and Neurotherapeutics, University of California, Davis, Davis, CA 95616, USA.
Yulong LiState Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
David A ProberTianqiao and Chrissy Chen Institute for Neuroscience, Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Dwight E BerglesSolomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD 21205, USA.
Mark C FishmanDepartment of Stem Cell and Regenerative Biology, Harvard University, Cambridge, MA 02138, USA.
Florian EngertDepartment of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA.
Misha B AhrensJanelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA. Electronic address: ahrensm@janelia.hhmi.org.

Funding

Zooming into the fish's brain-What is really going on! Connectomics analysis of larval zebrafish.U19NS104653 · NINDS · HARVARD UNIVERSITY · PI JOSHUA T VOGELSTEIN · 2017 to 2026
$39.4M
Murine Mutagenesis CoreP30NS050274 · NINDS · JOHNS HOPKINS UNIVERSITY · PI KOLODKIN, ALEX L · 2005 to 2020
$10.9M
Signaling to and from the SynapseP50MH084020 · NIMH · JOHNS HOPKINS UNIVERSITY · PI HUGANIR, RICHARD L · 2008 to 2012
$9.2M
Genetic and Neuronal Mechanisms that Regulate Zebrafish Sleep - DIVERSITY SUPPLEMENTR35NS122172 · NINDS · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI David Aaron Prober · 2021 to 2026
$6.1M
Training Program in NeuroscienceT32NS091018 · NINDS · JOHNS HOPKINS UNIVERSITY · PI JAMES J KNIERIM, Daniel Hans O'Connor · 2015 to 2026
$4.1M
Two-Photon All-Optical Electrophysiology in Behaving MiceRF1NS126043 · NINDS · HARVARD UNIVERSITY · PI COHEN, ADAM EZRA · 2022 to 2022
$2.2M
Design, Synthesis, and Evaluation of Neural Plasticity-Promoting Analogs of Iboga and Ergoline AlkaloidsR01GM128997 · NIGMS · UNIVERSITY OF CALIFORNIA AT DAVIS · PI OLSON, DAVID E · 2018 to 2022
$1.8M
Genetic and neural mechanisms underlying emerging social behavior in zebrafishR01NS124017 · NINDS · HARVARD UNIVERSITY · PI ENGERT, FLORIAN, FISHMAN, MARK C · 2024 to 2025
$1.5M
NIGMS NIH HHS R01 GM128997NIMH NIH HHS P50 MH084020NINDS NIH HHS P30 NS050274NINDS NIH HHS R01 NS124017NINDS NIH HHS R35 NS122172NINDS NIH HHS RF1 NS126043NINDS NIH HHS T32 NS091018NINDS NIH HHS U19 NS104653
6 · The paper itself

Abstract

Transient exposure to ketamine can trigger lasting changes in behavior and mood. We found that brief ketamine exposure causes long-term suppression of futility-induced passivity in larval zebrafish, reversing the "giving-up" response that normally occurs when swimming fails to cause forward movement. Whole-brain imaging revealed that ketamine hyperactivates the norepinephrine-astroglia circuit responsible for passivity. After ketamine washout, this circuit exhibits hyposensitivity to futility, leading to long-term increased perseverance. Pharmacological, chemogenetic, and optogenetic manipulations show that norepinephrine and astrocytes are necessary and sufficient for ketamine's long-term perseverance-enhancing aftereffects. In vivo calcium imaging revealed that astrocytes in adult mouse cortex are similarly activated during futility in the tail suspension test and that acute ketamine exposure also induces astrocyte hyperactivation. The cross-species conservation of ketamine's modulation of noradrenergic-astroglial circuits and evidence that plasticity in this pathway can alter the behavioral response to futility hold promise for identifying new strategies to treat affective disorders.

Indexed as

AstrocytesBehavior, AnimalExcitatory Amino Acid AntagonistsKetamineNeuronal PlasticityNorepinephrineAnimalsMiceMice, Inbred C57BLZebrafishExcitatory Amino Acid AntagonistsKetamineNorepinephrineastrocytesbehavioral statesbrain statescircuitsgliaketaminemood-altering compoundsnoradrenalinenorepinephrinezebrafish

Identifiers

PMID39694033
PMCPMC11889991

What OpenQuestion holds

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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.