Consolidation of Fear Extinction Requires Protein Synthesis in the Medial Prefrontal Cortex
Open accessAbstract
Extinction of conditioned fear is thought to form a long-term memory of safety, but the neural mechanisms are poorly understood. Consolidation of extinction learning in other paradigms requires protein synthesis, but the involvement of protein synthesis in extinction of conditioned fear remains unclear. Here, we show that rats infused intraventricularly with the protein synthesis inhibitor anisomycin extinguished normally within a session but were unable to recall extinction the following day. Anisomycin-treated rats showed no savings in the rate of re-learning of extinction, consistent with amnesia for extinction training. The identical effect was observed when anisomycin was microinfused into the medial prefrontal cortex (mPFC) but not the insular cortex. Furthermore, we observed that extinction training increased c-Fos levels in the mPFC but not in the insular cortex, consistent with extinction-induced gene expression in the mPFC. These findings extend previous lesion and unit-recording data by demonstrating that the mPFC is a critical storage site for extinction memory, rather than simply a pathway for expression of extinction. Understanding consolidation of fear extinction could lead to new treatments for anxiety disorders in which fear extinction is thought to be compromised.
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Translation of new protein is necessary for the formation of a novel threat extinction memory.
“This suggests that translation of new protein is necessary for the formation of a novel threat extinction memory [56].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [56]
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“Consistent with this, recall of extinction is correlated with plasticity in mPFC single units (Milad and Quirk, 2002), mPFC-evoked potentials (Herry and Garcia, 2002), and mPFC glucose utilization (Barrett et al.”
InfluentialSelf-citationThe role of ventromedial prefrontal cortex in the recovery of extinguished fear
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“Rats with lesions of the mPFC have difficulty recalling extinction learned the previous day (Morgan et al., 1993; Quirk et al., 2000; but see Gewirtz et al., 1997).”
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“Rats with lesions of the mPFC have difficulty recalling extinction learned the previous day (Morgan et al., 1993; Quirk et al., 2000; but see Gewirtz et al., 1997).”
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“…extinction 24 hr later (Quirk et al., 2000); (2) recall of extinction is inversely correlated with single-unit tone responses in the mPFC (Milad and Quirk, 2002), evoked potentials in the mPFC (Herry and Garcia, 2002), and glucose utilization in the mPFC (Barrett et al., 2003); and (3) stimulation…”
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- Authors
- Santini, E., Ge, H., Ren, K., de Ortiz, S. P., & Quirk, G. J.
- Affiliations
- Ponce Health Sciences University (PR)
- University of Puerto Rico at Río Piedras (PR)
- Corresponding author
- Quirk, Gregory J.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2004-06-23
- Volume
- 24
- Issue
- 25
- Pages
- 5704-5710
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6729226
- OpenAlex
- W2151571360
- Cited by
- 479
- References
- 9
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 12 · 2023: 13 · 2022: 6 · 2021: 9 · 2020: 15 · 2019: 15 · 2018: 20 · 2017: 18 · 2016: 21 · 2015: 24 · 2014: 15 · 2013: 36 · 2012: 29
- FWCI
- 18.04
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5s06gm008239-23, MH058883)
- National Institute of Mental Health (F31MH066575, R01MH058883)
- National Institute of General Medical Sciences (S06 GM-08239, S06-GM 008239)
- National Center for Research Resources (P20RR015565)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Keywords
- fear extinction, extinction memory consolidation, protein synthesis, medial prefrontal cortex, anisomycin, c-fos, insula, anxiety disorders, fear conditioning
- MeSH terms
- Animals, Anisomycin, Brain, Conditioning, Operant, Extinction, Psychological, Fear, Injections, Intraventricular, Male, Protein Synthesis Inhibitors, Mental Recall, Proto-Oncogene Proteins c-fos, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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