Evidence map›Paper›PMID 28017470›Full record

ArticleNeuron2017

A Central Amygdala CRF Circuit Facilitates Learning about Weak Threats.

Christina A Sanford, Marta E Soden, Madison A Baird, Samara M Miller, Jay Schulkin, Richard D Palmiter, Michael Clark, Larry S Zweifel

Open access · bronzeAbstract read
In one paragraph

Article in Neuron, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed
8.2field-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

132 citing papers in PubMed, 202 citations in OpenAlex.

  1. Trial
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  7. A neural circuit basis for reward-induced suppression of fear generalization and enhancement of fear extinction.Proceedings of the National Academy of Sciences of the United States of America · 2026
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  11. mWAKE in the Central Amygdala Regulates Fear Learning and Memory.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Article
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72 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

8 authors at 2 institutions in 1 country.

Christina A SanfordDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA.
Marta E SodenDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA.
Madison A BairdDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA.
Samara M MillerDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA.
Jay SchulkinDepartment of Physiology and Biophysics, Georgetown University, Washington, DC 20057, USA; Department of Neuroscience, Georgetown University, Washington, DC 20057, USA; Department of Obstetrics and Gynecology, University of Washington, Seattle, WA 98105, USA.
Richard D PalmiterDepartment of Biochemistry, University of Washington, Seattle, WA 98105, USA.
Michael ClarkDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98105, USA.
Larry S ZweifelDepartment of Pharmacology, University of Washington, Seattle, WA 98105, USA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98105, USA. Electronic address: larryz@uw.edu.
University of Washington · USGeorgetown University · US

Funding

Pharmacological Sciences SupplementT32GM007750 · NIGMS · UNIVERSITY OF WASHINGTON · PI ATKINS, WILLIAM M · 1985 to 2023
$12.6M
TRAINING IN THE MOLECULAR PHARMACOLOGY OF ABUSED DRUGST32DA007278 · NIDA · UNIVERSITY OF WASHINGTON · PI Susan Marie Ferguson, Paul E. M. Phillips · 1993 to 2026
$9.8M
Therapeutic Potential of Kappa Antagonists in the Adjunctive Treatment of Psychotic DepressionP50MH106428 · NIMH · UNIVERSITY OF WASHINGTON · PI CHAVKIN, CHARLES · 2015 to 2019
$7.6M
Functional Mapping of Dopamine-Dependent Fear Circuitry Through Advanced GeneticR01MH094536 · NIMH · UNIVERSITY OF WASHINGTON · PI ZWEIFEL, LARRY S · 2011 to 2015
$2.3M
Cell type-specific calcium imaging during hippocampus-dependent memoryR21MH098177 · NIMH · UNIVERSITY OF WASHINGTON · PI ZWEIFEL, LARRY S · 2012 to 2013
$417k
NIDA NIH HHS T32 DA007278NIMH NIH HHS P50 MH106428NIMH NIH HHS R01 MH094536NIMH NIH HHS R21 MH098177
6 · The paper itself

Abstract

Fear is a graded central motive state ranging from mild to intense. As threat intensity increases, fear transitions from discriminative to generalized. The circuit mechanisms that process threats of different intensity are not well resolved. Here, we isolate a unique population of locally projecting neurons in the central nucleus of the amygdala (CeA) that produce the neuropeptide corticotropin-releasing factor (CRF). CRF-producing neurons and CRF in the CeA are required for discriminative fear, but both are dispensable for generalized fear at high US intensities. Consistent with a role in discriminative fear, CRF neurons undergo plasticity following threat conditioning and selectively respond to threat-predictive cues. We further show that excitability of genetically isolated CRF-receptive (CRFR1) neurons in the CeA is potently enhanced by CRF and that CRFR1 signaling in the CeA is critical for discriminative fear. These findings demonstrate a novel CRF gain-control circuit and show separable pathways for graded fear processing.

Indexed as

AmygdalaAnimalsCentral Amygdaloid NucleusCorticotropin-Releasing HormoneCRF Receptor, Type 1FearLearningMiceMice, KnockoutNeuronsReceptors, Corticotropin-Releasing HormoneSynaptic TransmissionCorticotropin-Releasing HormoneCRF Receptor, Type 1Receptors, Corticotropin-Releasing Hormonecentral amygdalacircuitsCRFdifferential fear conditioningfearGABALTPplasticitythreat

Identifiers

PMID28017470
PMCPMC5217711
OpenAlexW2563744755

What OpenQuestion holds

Textmetadata
LicenceTDM
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.