Hippocampal and Prefrontal Projections to the Basal Amygdala Mediate Contextual Regulation of Fear after Extinction
Open accessAbstract
Knowing when and where to express fear is essential to survival. Recent work in fear extinction paradigms reveals that the contextual regulation of fear involves a neural network involving the hippocampus, medial prefrontal cortex, and amygdala. The amygdaloid basal nuclei (BA) receive convergent input from the ventral hippocampus (VH) and prelimbic (PL) prefrontal cortex and may integrate VH and PL input to regulate fear expression. To examine the functional organization of this neural circuit, we used cellular imaging of c-fos expression in anatomically defined neuronal populations and circuit disconnections to identify the pathways involved in the contextual control of extinguished fear. Before behavioral testing, we infused a retrograde tracer into the amygdala to label BA-projecting neurons in VH and PL. Rats then underwent fear conditioning and extinction and were tested for their fear to the extinguished conditioned stimulus (CS) in either the extinction context or in another context; freezing behavior served as the index of conditional fear. CS presentation outside the extinction context renewed conditional freezing and was associated with significantly more c-fos expression in BA-projecting neurons in the VH and PL than that induced by CS presentation in the extinction context. We next examined whether direct or indirect projections of VH to BA mediate fear renewal. Interestingly, disconnections of the VH from either the BA or PL eliminated renewal. These findings suggest that convergent inputs from both the VH and PL in the BA mediate the contextual control of fear after extinction.
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Disconnection of the vHPC from the mPFC interferes with renewal of threat memories.
“disconnection of the vHPC from the mPFC interferes with renewal of threat memories, a context-dependent process [43].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [43]
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Cites
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- Authors
- Orsini, C. A., Kim, J. H., Knapska, E., & Maren, S.
- Affiliations
- University of Michigan (US)
- Instytut Biologii Doświadczalnej im. Marcelego Nenckiego (PL)
- Corresponding author
- Maren, Stephen
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2011-11-23
- Volume
- 31
- Issue
- 47
- Pages
- 17269-17277
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC3241946
- OpenAlex
- W1992402923
- Cited by
- 315
- References
- 7
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 15 · 2023: 18 · 2022: 17 · 2021: 36 · 2020: 21 · 2019: 21 · 2018: 24 · 2017: 24 · 2016: 25 · 2015: 35 · 2014: 28 · 2013: 25 · 2012: 8
- FWCI
- 9.91
- 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)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institute of Mental Health (F31MH091822, 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, contextual fear, fear renewal, ventral hippocampus, prelimbic cortex, basal amygdala, Fos expression, retrograde tracing, circuit disconnection, fear conditioning
- MeSH terms
- Amygdala, Animals, Extinction, Psychological, Fear, Hippocampus, Male, Neural Pathways, Random Allocation, Prefrontal Cortex, Rats, Long-Evans, Rats
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