Evidence map›Paper›PMID 39693433›Full record

ArticleScience advances2024

Dynamic responses of striatal cholinergic interneurons control behavioral flexibility.

Zhenbo Huang, Ruifeng Chen, Matthew Ho, Xueyi Xie, Himanshu Gangal, Xuehua Wang, Jun Wang

Abstract read
In one paragraph

Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing 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

29 citing papers in PubMed.

  1. Article
  2. Article
  3. Chronic ethanol self-administration alters dopamine in the caudate nucleus and putamen of rhesus macaques in a sex-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Alcohol and Opioids Modulate Excitatory Inputs to the SCN.bioRxiv : the preprint server for biology · 2026
    Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Synchrony of neuromodulatory systems during NREM sleep.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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

7 authors.

Zhenbo HuangDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.ORCID 0000-0003-4857-5500
Ruifeng ChenDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Matthew HoDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Xueyi XieDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.ORCID 0000-0002-2349-1223
Himanshu GangalDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Xuehua WangDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.
Jun WangDepartment of Neuroscience and Experimental Therapeutics, College of Medicine, Texas A&M University Health Science Center, Bryan, TX, USA.ORCID 0000-0002-0085-4722

Funding

Ethanol drinking and the basal ganglia circuitryR01AA027768 · NIAAA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI WANG, JUN · 2020 to 2024
$2.0M
Striatal ensemble plasticity in alcohol use disorderR01AA030293 · NIAAA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI Jun Wang · 2023 to 2026
$1.8M
Synaptic Plasticity and Alcohol Use DisorderU01AA025932 · NIAAA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI WANG, JUN · 2017 to 2021
$1.6M
NIAAA NIH HHS R01 AA027768NIAAA NIH HHS R01 AA030293NIAAA NIH HHS U01 AA025932
6 · The paper itself

Abstract

Striatal cholinergic interneurons (CINs) are key to regulating behavioral flexibility, involving both extinguishing learned actions and adopting new ones. However, the mechanisms driving these processes remain elusive. In this study, we initially demonstrate that chronic alcohol consumption disrupts the burst-pause dynamics of CINs and impairs behavioral flexibility. We next aimed to elucidate the mechanisms by which CIN dynamics control behavioral flexibility. We found that extinction learning enhances acetylcholine (ACh) release and that mimicking this enhancement through optogenetic induction of CIN burst firing accelerates the extinction process. In addition, we demonstrate that disrupting CIN pauses via continuous optogenetic stimulation reversibly impairs the updating of goal-directed behaviors. Overall, we demonstrate that CIN burst firing, which increases ACh release, promotes extinction learning, aiding the extinguishment of learned behaviors. Conversely, CIN firing pauses, which lead to ACh dips, are crucial for reversal learning, facilitating the adaptation of new actions. These findings shed light on how CIN dynamics regulate behavioral flexibility.

Indexed as

AcetylcholineCholinergic NeuronsCorpus StriatumInterneuronsOptogeneticsAnimalsBehavior, AnimalExtinction, PsychologicalMaleMiceReversal LearningAcetylcholine

Identifiers

PMID39693433
PMCPMC11654678

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.