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Dissociable Roles of Prelimbic and Infralimbic Cortices, Ventral Hippocampus, and Basolateral Amygdala in the Expression and Extinction of Conditioned Fear

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Sierra-Mercado, Demetrio, Padilla-Coreano, Nancy, Quirk, Gregory J·2011·Neuropsychopharmacology

DOI 10.1038/npp.2010.184PMC PMC3005957

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Abstract

Current models of conditioned fear expression and extinction involve the basolateral amygdala (BLA), ventral medial prefrontal cortex (vmPFC), and the hippocampus (HPC). There is some disagreement with respect to the specific roles of these structures, perhaps due to subregional differences within each area. For example, growing evidence suggests that infralimbic (IL) and prelimbic (PL) subregions of vmPFC have opposite influences on fear expression. Moreover, it is the ventral HPC (vHPC), rather than the dorsal HPC, that projects to vmPFC and BLA. To help determine regional specificity, we used small doses of the GABA(A) agonist muscimol to selectively inactivate IL, PL, BLA, or vHPC in an auditory fear conditioning and extinction paradigm. Infusions were performed prior to extinction training, allowing us to assess the effects on both fear expression and subsequent extinction memory. Inactivation of IL had no effect on fear expression, but impaired the within-session acquisition of extinction as well as extinction memory. In contrast, inactivation of PL impaired fear expression, but had no effect on extinction memory. Inactivation of the BLA or vHPC impaired both fear expression and extinction memory. Post-extinction inactivations had no effect in any structure. We suggest a model in which amygdala-dependent fear expression is modulated by inputs from PL and vHPC, whereas extinction memory requires extinction-induced plasticity in IL, BLA, and/or vHPC.

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Authors: Sierra-Mercado, D., Padilla-Coreano, N., & Quirk, G. J.
Affiliations: University of Puerto Rico, Medical Sciences Campus (PR)
Corresponding author: Quirk, Gregory J
ORCID: Padilla-Coreano, Nancy
Quirk, Gregory J
Venue: Neuropsychopharmacology
Publisher: Springer Science and Business Media LLC
Published: 2010-10-20
Volume: 36
Issue: 2
Pages: 529-538
ISSN: 0893-133X (ISSN-L)
1740-634X
DOI: 10.1038/npp.2010.184
PMC: PMC3005957
OpenAlex: W2108888119
Cited by: 1,190
References: 78
Citations by year: 2026: 50 · 2025: 61 · 2024: 80 · 2023: 73 · 2022: 78 · 2021: 109 · 2020: 78 · 2019: 77 · 2018: 90 · 2017: 78 · 2016: 75 · 2015: 90 · 2014: 88 · 2013: 84 · 2012: 50
FWCI: 31.42
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
Locations: Neuropsychopharmacology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01mh081975-05)
National Institute of Mental Health (MH-058883, R01-MH081975, R01MH058883, R37MH058883, MH081975, R36MH089296, R29MH058883)
National Institute of General Medical Sciences (T34GM007821)
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 conditioning, fear extinction, infralimbic cortex, prelimbic cortex, ventral hippocampus, basolateral amygdala, ventromedial prefrontal cortex, auditory fear conditioning, muscimol inactivation, memory extinction
MeSH terms: Amygdala, Animals, Conditioning, Operant, Extinction, Psychological, Fear, Male, Rats, Sprague-Dawley, Prefrontal Cortex, Rats, CA1 Region, Hippocampal

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Dissociable Roles of Prelimbic and Infralimbic Cortices, Ventral Hippocampus, and Basolateral Amygdala in the Expression and Extinction of Conditioned Fear

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