Evidence map›Paper›PMID 34997190›Full record

ArticleMolecular psychiatry2022

Hippocampal acetylcholine modulates stress-related behaviors independent of specific cholinergic inputs.

Yann S Mineur, Tenna N Mose, Laura Vanopdenbosch, Ian M Etherington, Chika Ogbejesi, Ashraful Islam, Cristiana M Pineda, Richard B Crouse, Wenliang Zhou, David C Thompson and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular psychiatry, 2022. 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
3.5field-weighted citation impact, top 6% 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

32 citing papers in PubMed, 43 citations in OpenAlex.

  1. Effects ofInternational journal of molecular sciences · 2026
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  8. Article
  9. Anxiolytic Effects ofInternational journal of general medicine · 2026
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  13. Scopolamine induced learning deficit in marmosets.bioRxiv : the preprint server for biology · 2025
    Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. The identification of novel missense variant inOpen medicine (Warsaw, Poland) · 2025
    Article
  20. Medial prefrontal cortex acetylcholine signaling mediates the ability to learn an active avoidance response following learned helplessness training.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024
    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

12 authors at 1 institution in 1 country.

Yann S MineurDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Tenna N MoseDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Laura VanopdenboschDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Ian M EtheringtonDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Chika OgbejesiDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Ashraful IslamDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Cristiana M PinedaDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Richard B CrouseDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Wenliang ZhouDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
David C ThompsonDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Matthew P BenthamDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA.
Marina R PicciottoDepartment of Psychiatry, Yale University School of Medicine, 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA. marina.picciotto@yale.edu.ORCID http://orcid.org/0000-0002-4404-1280
Yale University · US

Funding

Yale-SCORE Resource Support CoreU54AA027989 · NIAAA · YALE UNIVERSITY · PI Kelly P Cosgrove · 2020 to 2026
$13.0M
Interdepartmental Neuroscience Program (INP)T32NS041228 · NINDS · YALE UNIVERSITY · PI Charles A Greer, Marina R Picciotto · 2001 to 2026
$12.0M
Cholinergic Contribution to Circuits Underlying DepressionR01MH077681 · NIMH · YALE UNIVERSITY · PI MINEUR, YANN SEBASTIEN, PICCIOTTO, MARINA R · 2006 to 2025
$7.0M
Yale SCOR on Gender-Sensitive Treatment for Tobacco DependenceP50DA033945 · NIDA · YALE UNIVERSITY · PI MCKEE, SHERRY ANN · 2012 to 2017
$6.5M
Acetylcholine signaling allows cognitive processes in the brain to regulate physiological responses to the environment: the example of central control of opiate toleranceDP1DA050986 · NIDA · YALE UNIVERSITY · PI PICCIOTTO, MARINA R · 2019 to 2023
$5.9M
NEUROBIOLOGY OF CORTICAL SYSTEMST32NS007224 · NINDS · YALE UNIVERSITY · PI CARDIN, JESSICA A · 1985 to 2025
$4.6M
Cholinergic Pathways in DepressionR03MH105824 · NIMH · YALE UNIVERSITY · PI MINEUR, YANN SEBASTIEN · 2015 to 2016
$167k
NIAAA NIH HHS U54 AA027989NIDA NIH HHS DP1 DA050986NIDA NIH HHS P50 DA033945NIMH NIH HHS R01 MH077681NIMH NIH HHS R03 MH105824NINDS NIH HHS T32 NS007224NINDS NIH HHS T32 NS041228
6 · The paper itself

Abstract

Acetylcholine (ACh) levels are elevated in actively depressed subjects. Conversely, antagonism of either nicotinic or muscarinic ACh receptors can have antidepressant effects in humans and decrease stress-relevant behaviors in rodents. Consistent with a role for ACh in mediating maladaptive responses to stress, brain ACh levels increase in response to stressful challenges, whereas systemically blocking acetylcholinesterase (AChE, the primary ACh degradative enzyme) elicits depression-like symptoms in human subjects, and selectively blocking AChE in the hippocampus increases relevant behaviors in rodents. We used an ACh sensor to characterize stress-evoked ACh release, then used chemogenetic, optogenetic and pharmacological approaches to determine whether cholinergic inputs from the medial septum/diagonal bands of Broca (MSDBB) or ChAT-positive neurons intrinsic to the hippocampus mediate stress-relevant behaviors in mice. Chemogenetic inhibition or activation of MSDBB cholinergic neurons did not result in significant behavioral effects, while inhibition attenuated the behavioral effects of physostigmine. In contrast, optogenetic stimulation of septohippocampal terminals or selective chemogenetic activation of ChAT-positive inputs to hippocampus increased stress-related behaviors. Finally, stimulation of sparse ChAT-positive hippocampal neurons increased stress-related behaviors in one ChAT-Cre line, which were attenuated by local infusion of cholinergic antagonists. These studies suggest that ACh signaling results in maladaptive behavioral responses to stress if the balance of signaling is shifted toward increased hippocampal engagement.

Indexed as

AcetylcholineAcetylcholinesteraseAnimalsCholine O-AcetyltransferaseCholinergic AgentsCholinergic NeuronsHippocampusHumansMiceAcetylcholineAcetylcholinesteraseCholine O-AcetyltransferaseCholinergic Agents

Identifiers

PMID34997190
PMCPMC9106825
OpenAlexW4206519775

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.