Reciprocal patterns of c-Fos expression in the medial prefrontal cortex and amygdala after extinction and renewal of conditioned fear
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After extinction of conditioned fear, memory for the conditioning and extinction experiences becomes context dependent. Fear is suppressed in the extinction context, but renews in other contexts. This study characterizes the neural circuitry underlying the context-dependent retrieval of extinguished fear memories using c-Fos immunohistochemistry. After fear conditioning and extinction to an auditory conditioned stimulus (CS), rats were presented with the extinguished CS in either the extinction context or a second context, and then sacrificed. Presentation of the CS in the extinction context yielded low levels of conditioned freezing and induced c-Fos expression in the infralimbic division of the medial prefrontal cortex, the intercalated nuclei of the amygdala, and the dentate gyrus (DG). In contrast, presentation of the CS outside of the extinction context yielded high levels of conditioned freezing and induced c-Fos expression in the prelimbic division of the medial prefrontal cortex, the lateral and basolateral nuclei of the amygdala, and the medial division of the central nucleus of the amygdala. Hippocampal areas CA1 and CA3 exhibited c-Fos expression when the CS was presented in either context. These data suggest that the context specificity of extinction is mediated by prefrontal modulation of amygdala activity, and that the hippocampus has a fundamental role in contextual memory retrieval.
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vmPFC activation during recall of extinction memory inhibits the amygdala and dampens fear expression.
“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 Knapska and Maren, 2009
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- Authors
- Knapska, E., & Maren, S.
- Affiliations
- University of Michigan (US)
- Venue
- Learning & Memory
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2009-07-24
- Volume
- 16
- Issue
- 8
- Pages
- 486-493
- ISSN
- 1072-0502 (ISSN-L)
- 1549-5485
- PMC
- PMC2726014
- OpenAlex
- W2152032880
- Cited by
- 264
- References
- 56
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 15 · 2023: 8 · 2022: 7 · 2021: 13 · 2020: 18 · 2019: 12 · 2018: 19 · 2017: 13 · 2016: 21 · 2015: 29 · 2014: 25 · 2013: 27 · 2012: 19
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Learning & Memory (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- Fundacja na rzecz Nauki Polskiej
- National Institutes of Health
- National Institute of Mental Health (R01MH065961)
- 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
- Fos expression, fear extinction, fear renewal, medial prefrontal cortex, amygdala, hippocampus, infralimbic cortex, prelimbic cortex, dentate gyrus, fear conditioning, auditory conditioned stimulus, conditioned freezing
- MeSH terms
- Amygdala, Analysis of Variance, Animals, Association Learning, Brain Mapping, Conditioning, Classical, Extinction, Psychological, Fear, Hippocampus, Immunohistochemistry, Male, Neural Pathways, Proto-Oncogene Proteins c-fos, Prefrontal Cortex, Rats, Long-Evans, Rats
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