Evidence map›Paper›PMID 41811445›Full record

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

Locus coeruleus-amygdala circuit disrupts prefrontal control to impair fear extinction.

Hugo Bayer, Annalise N Binette, Samantha O Sweck, Vitor A L Juliano, Samantha L Plas, Lara M Ferst, James E Hassell, Flávio A G Mourão, Stephen Maren

Abstract read
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 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Article
  2. Review
  3. Locus coeruleus-amygdala circuit disrupts prefrontal control to impair fear extinction.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. 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

9 authors.

Hugo Bayer *Beckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801.
Annalise N Binette *Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843.
Samantha O SweckDepartment of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843.
Vitor A L JulianoDepartment of Pharmacology, São Paulo University, São Paulo, SP 05508-000, Brazil.
Samantha L PlasBeckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801.ORCID 0000-0003-4282-6241
Lara M FerstBeckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801.ORCID 0000-0001-6199-9960
James E HassellDepartment of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843.
Flávio A G MourãoBeckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801.
Stephen MarenBeckman Institute for Advanced Science and Technology, University of Illinois Urbana-Champaign, Urbana, IL 61801.ORCID 0000-0002-9342-7411

Funding

Neural Substrates of Contextual Memory in Fear ExtinctionR01MH065961 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MAREN, STEPHEN · 2003 to 2025
$7.9M
Neural Circuits for Stress-Impaired Extinction LearningR01MH117852 · NIMH · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI Stephen Maren · 2018 to 2026
$4.6M
HHS | NIH | National Institute of Mental Health (NIMH) R01MH065961HHS | NIH | National Institute of Mental Health (NIMH) R01MH117852NIMH NIH HHS R01 MH065961NIMH NIH HHS R01 MH117852
6 · The paper itself

Abstract

Stress undermines extinction learning and hinders exposure-based clinical therapies for a variety of neuropsychiatric disorders. In both animals and humans, dysfunction in the ventromedial prefrontal cortex (vmPFC) contributes to stress-impaired extinction, but the neural circuit by which stress modulates vmPFC function is not known. We hypothesize that locus coeruleus (LC) norepinephrine undermines extinction learning by recruiting projections from the basolateral amygdala (BLA) to vmPFC. Using a combination of circuit-specific chemogenetics and calcium imaging, we find that activation of LC noradrenergic neurons mimics a behavioral stressor (footshock), induces freezing behavior, reduces spontaneous neuronal activity in the vmPFC, impairs extinction learning, and alters the population dynamics of vmPFC ensembles. Activation of LC also increases shock-induced responses in BLA neurons that project to vmPFC. Selective chemogenetic activation of LC→BLA projections impairs extinction; propranolol infusions into the BLA mitigate the effects of LC activation. Together, these results indicate that the BLA serves as a critical interface between the LC and mPFC to mediate stress-induced extinction impairments.

Indexed as

AmygdalaExtinction, PsychologicalFearLocus CoeruleusPrefrontal CortexAnimalsBasolateral Nuclear ComplexMaleNeural PathwaysNorepinephrineStress, PsychologicalNorepinephrinebasolateral amygdalaextinctionlocus coeruleusprefrontal cortexstress

Identifiers

PMID41811445
PMCPMC12993942

What OpenQuestion holds

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LicenceCC BY-NC-ND
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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.