Evidence map›Paper›PMID 41785321›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Fear extinction induces maladaptive generalization via noradrenergic and GABAergic systems.

Aiqiu Zheng, Dan Yu, Xin Meng, Shumin Gong, Jiale Ye, Hui Zhou, Mo Chen, Shuming An, Jun Ma, Can Li and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

12 authors.

Aiqiu Zheng *Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.ORCID 0009-0000-1252-6198
Dan Yu *Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Xin Meng *Jiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Shumin GongJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Jiale YeJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Hui ZhouJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Mo ChenJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.ORCID 0000-0001-7378-297X
Shuming AnJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Jun MaJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Can LiDepartment of Pathogen Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Jiangsu International Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.ORCID 0000-0002-8420-120X
Jun-Li CaoJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.ORCID 0000-0002-8932-4743
Kunwei WuJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesiology and Brain Science, National Medical Products Administration Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, School of Anesthesiology, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.ORCID 0000-0003-4074-0567

Funding

Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (Key University of Science Research Project of Jiangsu Province) 24KJA320007MOST | National Natural Science Foundation of China (NSFC) 82293641MOST | National Natural Science Foundation of China (NSFC) 82401511
6 · The paper itself

Abstract

Exposure therapy for anxiety disorders relies on fear extinction to reduce pathological fear responses. Here, we show that while effective at diminishing conditioned fear, extinction training paradoxically enhances fear generalization to safe stimuli through activation of the locus coeruleus-dentate gyrus (LC-DG) noradrenergic circuit. Specifically, LC norepinephrine release during extinction stimulates DG GABAergic neurons via β1-adrenergic receptors, engaging a PKA/CREB-dependent signaling cascade that ultimately leads to α4-GABA

Indexed as

Extinction, PsychologicalFearGABAergic NeuronsGeneralization, PsychologicalNorepinephrineAnimalsCyclic AMP-Dependent Protein KinasesDentate GyrusLocus CoeruleusMaleMiceReceptors, Adrenergic, beta-1Receptors, GABA-ASignal TransductionCyclic AMP-Dependent Protein KinasesNorepinephrineReceptors, Adrenergic, beta-1Receptors, GABA-Aanxietyfear memoryGABAA receptorslocus coeruleusPTSD

Identifiers

PMID41785321
PMCPMC12974448

What Socratic holds

Textmetadata
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 Socratic graph.