Evidence map›Paper›PMID 41985453›Full record

ArticleNeuron2026

Dual-engram architecture within a single striatal cell type distinctly controls alcohol relapse and extinction.

Xueyi Xie, Yufei Huang, Ruifeng Chen, Zhenbo Huang, Himanshu Gangal, Ziyi Li, Jiayi Lu, Adelis M Cruz, Anita Chaiprasert, Emily Yu and 6 more

Abstract read
In one paragraph

Article in Neuron, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 citing papers in PubMed.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors.

Xueyi XieDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Yufei HuangDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA; Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA.
Ruifeng ChenDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Zhenbo HuangDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Himanshu GangalDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA; Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA.
Ziyi LiDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA; Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA.
Jiayi LuDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Adelis M CruzDepartment of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843, USA.
Anita ChaiprasertDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Emily YuDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Nicholas HernandezDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Valerie VierkantDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Runmin WangDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Xuehua WangDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA.
Rachel J SmithInstitute for Neuroscience, Texas A&M University, College Station, TX 77843, USA; Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843, USA.
Jun WangDepartment of Neuroscience and Experimental Therapeutics, Naresh K. Vashisht College of Medicine, Texas A&M University Health Science Center, Bryan, TX 77807, USA; Institute for Neuroscience, Texas A&M University, College Station, TX 77843, USA. Electronic address: jwang188@tamu.edu.

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
Establishing a link between habits and punishment resistanceR01DA046457 · NIDA · TEXAS A&M UNIVERSITY · PI SMITH, RACHEL J · 2019 to 2023
$1.8M
Synaptic Plasticity and Alcohol Use DisorderU01AA025932 · NIAAA · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · PI WANG, JUN · 2017 to 2021
$1.6M
Ethanol and glutamatergic transmission in the dorsal striatumR01AA021505 · NIAAA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI WANG, JUN · 2012 to 2016
$1.4M
NIAAA NIH HHS R01 AA021505NIAAA NIH HHS R01 AA027768NIAAA NIH HHS R01 AA030293NIAAA NIH HHS U01 AA025932NIDA NIH HHS R01 DA046457
6 · The paper itself

Abstract

Relapse remains a major obstacle in treating alcohol and drug addiction and is thought to be driven by persistent drug-associated memories formed during use. Extinction training reduces relapse and is proposed to generate a competing memory, yet where and how these opposing memories are stored is unknown. Here, we show that two anatomically and functionally distinct engram ensembles within the same striatal cell type, direct-pathway medium spiny neurons (dMSNs), encode these opposing memories in mice. Operant alcohol learning recruits a broadly distributed dMSN ensemble that encodes relapse-promoting alcohol memories. By contrast, operant extinction recruits a striosome-enriched dMSN ensemble that encodes an extinction memory to suppress relapse. We further demonstrate that relapse-promoting memory is embedded in persistently strengthened corticostriatal synapses engaged during learning and that mimicking this synaptic strengthening is sufficient to drive relapse-like behavior. Together, these findings reveal a dual-engram architecture within dorsostriatal dMSNs governing relapse and extinction.

Indexed as

AlcoholismCorpus StriatumExtinction, PsychologicalAnimalsConditioning, OperantEthanolMaleMedium Spiny NeuronsMemoryMiceMice, Inbred C57BLRecurrenceEthanolalcohol relapsealcohol use disorderArcTRAPcorticostriatal synaptic plasticitydMSNsdorsomedial striatumengram ensembleextinction learningMOR-expressing striosomesoperant self-administration

Identifiers

PMID41985453
PMCPMC13094717

What OpenQuestion holds

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Registered trials

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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.