Prefrontal inputs to the amygdala instruct fear extinction memory formation
Open accessAbstract
Persistent anxiety after a psychological trauma is a hallmark of many anxiety disorders. However, the neural circuits mediating the extinction of traumatic fear memories remain incompletely understood. We show that selective, in vivo stimulation of the ventromedial prefrontal cortex (vmPFC)-amygdala pathway facilitated extinction memory formation, but not retrieval. Conversely, silencing the vmPFC-amygdala pathway impaired extinction formation and reduced extinction-induced amygdala activity. Our data demonstrate a critical instructional role for the vmPFC-amygdala circuit in the formation of extinction memories. These findings advance our understanding of the neural basis of persistent fear, with implications for posttraumatic stress disorder and other anxiety disorders.
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Reciprocal connections between the BLA and mPFC are important for fear extinction, fear discrimination, and other processes requiring the resolution of conflicting information.
“Reciprocal connections between the BLA and mPFC are important for fear extinction, fear discrimination, and other processes requiring the resolution of conflicting information (47–50), and dendritic hypotrophy in mPFC neurons has been linked to stress and alcohol-related deficits in fear extinction (51,52).”
From Chronic Stress Remodels Synapses in an Amygdala Circuit-Specific Manner (2019) · cites this paper as [50]
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- Authors
- Bukalo, O., Pinard, C. R., Silverstein, S., Brehm, C., Hartley, N. D., Whittle, N., Colacicco, G., Busch, E., Patel, S., Singewald, N., & Holmes, A.
- Affiliations
- National Institutes of Health (US)
- Universität Innsbruck (AT)
- Vanderbilt University Medical Center (US)
- Corresponding author
- Bukalo, Olena
- ORCID
- Venue
- Science Advances
- Published
- 2015-07-03
- Volume
- 1
- Issue
- 6
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC4618669
- OpenAlex
- W2258511068
- Cited by
- 234
- References
- 48
- Citations by year
- 2026: 14 · 2025: 26 · 2024: 19 · 2023: 25 · 2022: 24 · 2021: 24 · 2020: 22 · 2019: 26 · 2018: 25 · 2017: 13 · 2016: 11 · 2015: 5
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Minerva Access (University of Melbourne) (submittedVersion, cc-by-nc)
- Funders
- NIAAA intramural (ID0EDQAK2179)
- Department of Defense in the Center for Neuroscience and Regenerative Medicine (ID0E4WAK2180)
- Austrian Science Fund (ID0EX4AK2181, P25375)
- Sonderforschungsbereich (ID0E2EBK2182, SFB F4410-B19)
- National Institutes of Health (ID0E6LBK2183, MH103515, ID0EQMBK2184, T32 MH064913, ID0EBNBK2185, ID0ESNBK2186, MH090412)
- National Institutes on Health (ID0EDOBK2187, T32 MH064913)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory Processes and Influences
- Social Sciences › Psychology › Clinical Psychology › Posttraumatic Stress Disorder Research
- Keywords
- fear extinction, ventromedial prefrontal cortex, amygdala, neural circuits, anxiety disorders, post-traumatic stress disorder, neural silencing
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