Dissociable roles of prelimbic and infralimbic cortices, ventral hippocampus, and basolateral amygdala in the expression and extinction of conditioned fear
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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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Stimulation of infralimbic region inhibits fear expression.
“Thus, stimulation of the infralimbic region should inhibit fear expression, and it does (Sierra-Mercado, Padilla-Coreano, & Quirk, 2011).”
From Learned helplessness at fifty: Insights from neuroscience. (2016) · cites this paper as Sierra-Mercado, Padilla-Coreano, & Quirk, 2011
The Discussion (‘Fear expression: PL not IL’; page unavailable) suggests that IL helps inhibit fear responses during extinction. But the Results report inactivation, not stimulation: IL inactivation did not change freezing at the start of the session, though it impaired extinction. The paper therefore does not demonstrate that stimulating IL inhibits initial fear expression. (LLM, conf=0.83)
Experimental — accuracy not yet measuredThe vmPFC is not generally required for fear extinction.
“Neither is vmPFC generally required for fear extinction (but see [36]), in which cues are presented without reinforcement and the CR diminishes over time [34].”
From Ventromedial prefrontal–subcortical systems and the generation of affective meaning (2012) · cites this paper as [36]
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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
- Venue
- Neuropsychopharmacology
- Published
- 2010-10-20
- Volume
- 36
- Issue
- 2
- Pages
- 529-538
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- 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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