The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
Neurons in medial prefrontal cortex signal memory for fear extinction
Abstract
Conditioned fear responses to a tone previously paired with a shock diminish if the tone is repeatedly presented without the shock, a process known as extinction. Since Pavlov it has been hypothesized that extinction does not erase conditioning, but forms a new memory. Destruction of the ventral medial prefrontal cortex, which consists of infralimbic and prelimbic cortices, blocks recall of fear extinction, indicating that medial prefrontal cortex might store long-term extinction memory. Here we show that infralimbic neurons recorded during fear conditioning and extinction fire to the tone only when rats are recalling extinction on the following day. Rats that froze the least showed the greatest increase in infralimbic tone responses. We also show that conditioned tones paired with brief electrical stimulation of infralimbic cortex elicit low freezing in rats that had not been extinguished. Thus, stimulation resembling extinction-induced infralimbic tone responses is able to simulate extinction memory. We suggest that consolidation of extinction learning potentiates infralimbic activity, which inhibits fear during subsequent encounters with fear stimuli.
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In the citing paper
“vmPFC activation during recall of extinction memory inhibits the amygdala and dampens fear expression”
From Childhood adversity and neural development: Deprivation and threat as distinct dimensions of early experience (2014) · cites this paper as Milad and Quirk, 2002
In the citing paper
“This hypothesis was based on evidence that PFC (1) is critical for extinction retention (Herry and Garcia, 2003;Quirk et al, 2000;Milad and Quirk, 2002)”
From Impaired Extinction Retention in Adolescent Rats: Effects of D-Cycloserine (2010) · cites this paper as Milad and Quirk, 2002
In the citing paper
“A number of studies on rats suggest that activity in PrL underlies the expression of conditioned fear (27, 40, 41), whereas activity in IL underlies the extinction of conditioned fear (10, 27, 41, 42).”
From Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders (2012) · cites this paper as [10]
In the citing paper
“fear extinction studies suggest that both rat IL (10, 22, 27, 41, 42) and primate vmPFC (12, 15, 43) play a significant role in the successful recall of fear extinction.”
From Functional anatomy of ventromedial prefrontal cortex: implications for mood and anxiety disorders (2012) · cites this paper as [10]
In the citing paper
“Consistent with previous resting-state functional connectivity studies14,15 and effective connectivity studies,17,54 we found anticorrelations between the amygdala and medial prefrontal regions, including the dorsal and rostral ACC, consistent with our a priori hypothesis.”
From Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder (2012) · cites this paper as [54]
In the citing paper
“Such a lack of inhibition from dorsal medial regions to the amygdala can be interpreted as a deficit in automatic emotion regulation10 or a lack of cognitive control over emotion.54”
From Altered resting-state amygdala functional connectivity in men with posttraumatic stress disorder (2012) · cites this paper as [54]
In the citing paper
“electrical stimulation of infralimbic cortex reduces freezing to the CS even in animals that are resistant to extinction training108,112.”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [108]
In the citing paper
“increased activity in the infralimbic cortex is associated with fear extinction108”
From Resolving the neural circuits of anxiety (2015) · cites this paper as [108]
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Flagged first, then by citations
Research works printed but not linked: 1
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Cited by
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“Electrical stimulation of this region, which has direct inhibitory projections to the amygdala (107, 108), facilitates fear extinction (109).”
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“Furthermore, neural activity increases in the mPFC as extinction is learned (Milad and Quirk, 2002; Rosenkranz et al., 2003), and electrical sitmulation of mPFC can facilitate extinction learning (Milad et al., 2004).”
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“The ventromedial prefrontal cortex (vmPFC) has been shown to be important for the successful recall of the extinction (Milad & Quirk, 2002; Morgan, Romanski, & LeDoux, 1993; Quirk, Russo, Barron, & Lebron, 2000), with the magnitude of vmPFC activation (Milad et al., 2007) and the cortical thickness…”
Metadata
- Authors
- Milad, M. R., & Quirk, G. J.
- Affiliations
- Ponce Health Sciences University (PR)
- Corresponding author
- Quirk, Gregory J.
- Venue
- Nature
- Published
- 2002-11
- Volume
- 420
- Issue
- 6911
- Pages
- 70-74
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1989045560
- Cited by
- 1,836
- References
- 30
- Citations by year
- 2026: 40 · 2025: 55 · 2024: 73 · 2023: 59 · 2022: 58 · 2021: 82 · 2020: 75 · 2019: 88 · 2018: 90 · 2017: 80 · 2016: 102 · 2015: 95 · 2014: 95 · 2013: 121 · 2012: 88
- FWCI
- 23.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Science Foundation
- National Institute of Mental Health
- National Institute of General Medical Sciences
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- fear extinction, medial prefrontal cortex, infralimbic cortex, prelimbic cortex, memory extinction, fear conditioning, memory consolidation, neuronal firing, electrical stimulation, freezing behavior, rats
- MeSH terms
- Acoustic Stimulation, Animals, Conditioning, Classical, Electroshock, Extinction, Psychological, Fear, Male, Memory, Neurons, Sound, Rats, Sprague-Dawley, Prefrontal Cortex, Rats
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