Dopamine-dependent prefrontal reactivations explain long-term benefit of fear extinction
Open accessAbstract
Fear extinction does not prevent post-traumatic stress or have long-term therapeutic benefits in fear-related disorders unless extinction memories are easily retrieved at later encounters with the once-threatening stimulus. Previous research in rodents has pointed towards a role for spontaneous prefrontal activity occurring after extinction learning in stabilizing and consolidating extinction memories. In other memory domains spontaneous post-learning activity has been linked to dopamine. Here, we show that a neural activation pattern — evoked in the ventromedial prefrontal cortex (vmPFC) by the unexpected omission of the feared outcome during extinction learning — spontaneously reappears during postextinction rest. The number of spontaneous vmPFC pattern reactivations predicts extinction memory retrieval and vmPFC activation at test 24 h later. Critically, pharmacologically enhancing dopaminergic activity during extinction consolidation amplifies spontaneous vmPFC reactivations and correspondingly improves extinction memory retrieval at test. Hence, a spontaneous dopamine-dependent memory consolidation-based mechanism may underlie the long-term behavioral effects of fear extinction.
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- Authors
- Gerlicher, A. M. V., Tüscher, O., & Kalisch, R.
- Affiliations
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Corresponding author
- Gerlicher, A. M. V.
- Venue
- Nature Communications
- Published
- 2018-10-16
- Volume
- 9
- Issue
- 1
- Pages
- 4294-4294
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC6191435
- OpenAlex
- W2896619466
- Cited by
- 103
- References
- 7
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 14 · 2023: 14 · 2022: 15 · 2021: 17 · 2020: 11 · 2019: 14
- FWCI
- 6.25
- Type
- journal article
- Language
- en
- Update notices
- correction (2019-01-23)
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion, cc-by)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Deutsche Forschungsgemeinschaft (sub-project C04, subproject C01, CRC--1193)
- 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 › Neurotransmitter Receptor Influence on Behavior
- Keywords
- fear extinction, dopamine, ventromedial prefrontal cortex, spontaneous neuronal activity, memory consolidation, extinction consolidation, fear-related disorders, post-traumatic stress
- MeSH terms
- Memory Consolidation, Administration, Oral, Adult, Dopamine, Extinction, Psychological, Fear, Humans, Magnetic Resonance Imaging, Male, Prefrontal Cortex, Nontherapeutic Human Experimentation
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