Functional anatomy of neural circuits regulating fear and extinction
Open accessAbstract
The memory of fear extinction is context dependent: fear that is suppressed in one context readily renews in another. Understanding of the underlying neuronal circuits is, therefore, of considerable clinical relevance for anxiety disorders. Prefrontal cortical and hippocampal inputs to the amygdala have recently been shown to regulate the retrieval of fear memories, but the cellular organization of these projections remains unclear. By using anterograde tracing in a transgenic rat in which neurons express a dendritically-targeted PSD-95:Venus fusion protein under the control of a c- fos promoter, we found that, during the retrieval of extinction memory, the dominant input to active neurons in the lateral amygdala was from the infralimbic cortex, whereas the retrieval of fear memory was associated with greater hippocampal and prelimbic inputs. This pattern of retrieval-related afferent input was absent in the central nucleus of the amygdala. Our data show functional anatomy of neural circuits regulating fear and extinction, providing a framework for therapeutic manipulations of these circuits.
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The expression and inhibition of learned fear is largely regulated by the amygdala, hippocampus, and PFC in adult rodents and humans.
“The expression and inhibition of learned fear is largely regulated by the amygdala, hippocampus, and PFC in adult rodents and humans (Knapska et al., 2012;LeDoux, 2003;Maren and Quirk, 2004;Tovote et al., 2015)”
From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Knapska et al., 2012
The introduction identifies the amygdala, hippocampus, and prefrontal cortex as the three main structures involved in auditory fear extinction and describes their differing effects on fear expression. The Methods identify the study subjects as rats. The paper notes clinical relevance to human anxiety disorders but does not establish the claimed regulation in humans (page numbers unavailable). (LLM, conf=0.86)
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Cites
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- Authors
- Knapska, E., Macias, M., Mikosz, M., Nowak, A., Owczarek, D., Wawrzyniak, M., Pieprzyk, M., Cymerman, I. A., Werka, T., Sheng, M., Maren, S., Jaworski, J., & Kaczmarek, L.
- Affiliations
- Departments of aNeurophysiology and
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- International Institute of Molecular and Cell Biology (PL)
- Massachusetts Institute of Technology (US)
- Texas A&M University (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2012-10
- Volume
- 109
- Issue
- 42
- Pages
- 17093-17098
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3479515
- OpenAlex
- W2120495407
- Cited by
- 187
- References
- 7
- Citations by year
- 2026: 5 · 2025: 6 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 23 · 2020: 12 · 2019: 14 · 2018: 20 · 2017: 13 · 2016: 12 · 2015: 17 · 2014: 21 · 2013: 16
- FWCI
- 8.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- OakTrust (Texas A&M University Libraries) (submittedVersion)
- Funders
- European Commission
- Fundacja na rzecz Nauki Polskiej
- National Institutes of Health
- Narodowe Centrum Badań i Rozwoju
- National Institute of Mental Health (R01MH065961)
- 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, fear memory, neural circuits, lateral amygdala, infralimbic cortex, hippocampus, prelimbic cortex, central amygdala, memory retrieval, anxiety disorders, c-fos, anterograde tracing, contextual memory
- MeSH terms
- Disks Large Homolog 4 Protein, Amygdala, Analysis of Variance, Animals, Bacterial Proteins, Conditioning, Psychological, Extinction, Psychological, Fear, Image Processing, Computer-Assisted, Immunohistochemistry, Limbic System, Luminescent Proteins, Male, Membrane Proteins, Memory, Neural Pathways, Recombinant Fusion Proteins, Video Recording, DNA Primers, Microscopy, Confocal, Intracellular Signaling Peptides and Proteins, Rats, Rats, Transgenic
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