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Cited by 53Memory and Neural MechanismsNeuroscience and Neuropharmacology ResearchNeurotransmitter Receptor Influence on Behavior

Persistent activation of central amygdala CRF neurons helps drive the immediate fear extinction deficit

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Jo, Yong S., Namboodiri, Vijay Mohan K., Stuber, Garret D., Zweifel, Larry S.·2020·Nature Communications
DOI 10.1038/s41467-020-14393-yPMC PMC6976644
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Abstract

Fear extinction is an active learning process whereby previously established conditioned responses to a conditioned stimulus are suppressed. Paradoxically, when extinction training is performed immediately following fear acquisition, the extinction memory is weakened. Here, we demonstrate that corticotrophin-releasing factor (CRF)-expressing neurons in the central amygdala (CeA) antagonize the extinction memory following immediate extinction training. CeA-CRF neurons transition from responding to the unconditioned stimulus to the conditioned stimulus during the acquisition of a fear memory that persists during immediate extinction training, but diminishes during delayed extinction training. Inhibition of CeA-CRF neurons during immediate extinction training is sufficient to promote enhanced extinction memories, and activation of these neurons following delay extinction training is sufficient to reinstate a previously extinguished fear memory. These results demonstrate CeA-CRF neurons are an important substrate for the persistence of fear and have broad implications for the neural basis of persistent negative affective behavioral states.

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Authors
Jo, Y. S., Namboodiri, V. M. K., Stuber, G. D., & Zweifel, L. S.
Affiliations
  • Korea University (KR)
  • University of Washington (US)
Corresponding author
Zweifel, Larry S.
ORCID
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2020-01-22
Volume
11
Issue
1
Pages
422-422
ISSN
2041-1723 (ISSN-L)
DOI
10.1038/s41467-020-14393-y
PMC
PMC6976644
OpenAlex
W3001327843
Cited by
53
References
41
Citations by year
2026: 6 · 2025: 7 · 2024: 12 · 2023: 8 · 2022: 9 · 2021: 6 · 2020: 4 · 2019: 1
FWCI
3.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Communications (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (R37 DA032750)
  • U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (P50MH10642)
Topics
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
fear extinction, central amygdala, memory extinction, negative emotions, fear conditioning
MeSH terms
Animals, Behavior, Animal, Conditioning, Psychological, Corticotropin-Releasing Hormone, Extinction, Psychological, Fear, Female, Male, Memory, Neurons, Central Amygdaloid Nucleus

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