Evidence map›Paper›PMID 35856493›Full record

ArticleeLife2022

Dopamine D2Rs coordinate cue-evoked changes in striatal acetylcholine levels.

Kelly M Martyniuk, Arturo Torres-Herraez, Daniel C Lowes, Marcelo Rubinstein, Marie A Labouesse, Christoph Kellendonk

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

16 citing papers in PubMed, 19 citations in OpenAlex.

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  9. Inhibition of striatal indirect pathway during second postnatal week leads to long-lasting deficits in motivated behavior.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2025
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  11. The Aggregation ofBiomedicines · 2024
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  13. Dopamine D2 receptors in nucleus accumbens cholinergic interneurons increase impulsive choice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023
    Article
  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

6 authors at 4 institutions in 3 countries.

Kelly M MartyniukDepartment of Neuroscience, Columbia University, New York, United States.ORCID 0000-0003-4190-4121
Arturo Torres-HerraezDepartment of Psychiatry, Columbia University, New York, United States.
Daniel C LowesDepartment of Psychiatry, Columbia University, New York, United States.
Marcelo RubinsteinInstituto de Investigaciones en Ingeniería Genética y Biología Molecular, Consejo Nacional de Investigaciones Científicas y Técnicas, and Departamento de Fisiología, Biología Molecular y Celular, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
Marie A LabouesseDepartment of Psychiatry, Columbia University, New York, United States.ORCID 0000-0002-6850-5852
Christoph KellendonkDepartment of Psychiatry, Columbia University, New York, United States.ORCID 0000-0003-3302-2188
New York Psychoanalytic Society and Institute · USColumbia University · USETH Zurich · CHUniversidad de Buenos Aires · AR

Funding

Medium Spiny Neuron Excitability and MotivationR01MH093672 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI KELLENDONK, CHRISTOPH · 2011 to 2020
$5.0M
Co-Regulation of Striatal Dopamine and Acetylcholine During Flexible LearningR01MH124858 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI KELLENDONK, CHRISTOPH · 2021 to 2025
$2.7M
Striatal Regulation of Cortical Acetylcholine ReleaseR21MH126380 · NIMH · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI KELLENDONK, CHRISTOPH · 2022 to 2023
$430k
Co-regulation of striatal dopamine and acetylcholine in associative reward learningF99NS120642 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI MARTYNIUK, KELLY · 2021 to 2021
$47k
NIMH NIH HHS R01 MH093672NIMH NIH HHS R01 MH124858NIMH NIH HHS R21 MH126380NINDS NIH HHS F99 NS120642
6 · The paper itself

Abstract

In the striatum, acetylcholine (ACh) neuron activity is modulated co-incident with dopamine (DA) release in response to unpredicted rewards and reward-predicting cues and both neuromodulators are thought to regulate each other. While this co-regulation has been studied using stimulation studies, the existence of this mutual regulation in vivo during natural behavior is still largely unexplored. One long-standing controversy has been whether striatal DA is responsible for the induction of the cholinergic pause or whether DA D2 receptors (D2Rs) modulate a pause that is induced by other mechanisms. Here, we used genetically encoded sensors in combination with pharmacological and genetic inactivation of D2Rs from cholinergic interneurons (CINs) to simultaneously measure ACh and DA levels after CIN D2R inactivation in mice. We found that CIN D2Rs are not necessary for the initiation of cue-induced decrease in ACh levels. Rather, they prolong the duration of the decrease and inhibit ACh rebound levels. Notably, the change in cue-evoked ACh levels is not associated with altered cue-evoked DA release. Moreover, D2R inactivation strongly decreased the temporal correlation between DA and ACh signals not only at cue presentation but also during the intertrial interval pointing to a general mechanism by which D2Rs coordinate both signals. At the behavioral level D2R antagonism increased the latency to lever press, which was not observed in CIN-selective D2R knock out mice. Press latency correlated with the cue-evoked decrease in ACh levels and artificial inhibition of CINs revealed that longer inhibition shortens the latency to press compared to shorter inhibition. This supports a role of the ACh signal and it's regulation by D2Rs in the motivation to initiate actions.

Indexed as

AcetylcholineCorpus StriatumReceptors, Dopamine D2AnimalsCholinergic AgentsCuesDopamineMiceAcetylcholineCholinergic AgentsDopamineReceptors, Dopamine D2acetylcholinecircuitdopaminemotivationmouseneuromodulationneurosciencestriatum

Identifiers

PMID35856493
PMCPMC9363114
OpenAlexW4286210245

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.