Evidence map›Paper›PMID 29593511›Full record

ReviewFrontiers in behavioral neuroscience2018

Noradrenergic Modulation of Fear Conditioning and Extinction.

Thomas F Giustino, Stephen Maren

Open access · goldAbstract readReview
In one paragraph

Review in Frontiers in behavioral neuroscience, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 1 pooled it
10.2field-weighted citation impact, top 1% 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

103 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Alpha-2 Adrenoreceptor Antagonist Yohimbine Potentiates Consolidation of Conditioned Fear.The international journal of neuropsychopharmacology · 2022
    Trial
  4. Trial
  5. Trial
  6. Review
  7. Article
  8. Review
  9. Repeated restraint stress enhances visual plasticity through locus coeruleus (LC)-V1 projection in adult mice.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  10. Impact of early locus coeruleus lesions in the TgF344 Alzheimer's disease rat model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. 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
  12. Fear extinction induces maladaptive generalization via noradrenergic and GABAergic systems.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  13. Article
  14. Article
  15. Article
  16. Stimulus-Dependent Dopamine Dynamics from Locus Coeruleus Axons.bioRxiv : the preprint server for biology · 2025
    Article
  17. Article
  18. Article
  19. Article
  20. Article

43 more citing papers are in PubMed but not listed here.

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

2 authors at 1 institution in 1 country.

Thomas F GiustinoDepartment of Psychological and Brain Sciences, Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, United States.
Stephen MarenDepartment of Psychological and Brain Sciences, Texas A&M Institute for Neuroscience, Texas A&M University, College Station, TX, United States.
Texas A&M University · US

Funding

Neural Substrates of Contextual Memory in Fear ExtinctionR01MH065961 · NIMH · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MAREN, STEPHEN · 2003 to 2025
$7.9M
Noradrenergic modulation of stress-induced deficits in fear extinctionF31MH112208 · NIMH · TEXAS A&M UNIVERSITY · PI GIUSTINO, THOMAS · 2017 to 2018
$68k
6 · The paper itself

Abstract

The locus coeruleus norepinephrine (LC-NE) system plays a broad role in learning and memory. Here we begin with an overview of the LC-NE system. We then consider how both direct and indirect manipulations of the LC-NE system affect cued and contextual aversive learning and memory. We propose that NE dynamically modulates Pavlovian conditioning and extinction, either promoting or impairing learning aversive processes under different levels of behavioral arousal. We suggest that under high levels of stress (e.g., during/soon after fear conditioning) the locus coeruleus (LC) promotes cued fear learning by enhancing amygdala function while simultaneously blunting prefrontal function. Under low levels of arousal, the LC promotes PFC function to promote downstream inhibition of the amygdala and foster the extinction of cued fear. Thus, LC-NE action on the medial prefrontal cortex (mPFC) might be described by an inverted-U function such that it can either enhance or hinder learning depending on arousal states. In addition, LC-NE seems to be particularly important for the acquisition, consolidation and extinction of contextual fear memories. This may be due to dense adrenoceptor expression in the hippocampus (HPC) which encodes contextual information, and the ability of NE to regulate long-term potentiation (LTP). Moreover, recent work reveals that the diversity of LC-NE functions in aversive learning and memory are mediated by functionally heterogeneous populations of LC neurons that are defined by their projection targets. Hence, LC-NE function in learning and memory is determined by projection-specific neuromodulation that accompanies various states of behavioral arousal.

Indexed as

consolidationextinctionfearlocus coeruleusnorepinephrine

Identifiers

PMID29593511
PMCPMC5859179
OpenAlexW2790904219

What OpenQuestion holds

Textmetadata
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.