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Distinct hippocampal engrams control extinction and relapse of fear memory
Open accessAbstract
Learned fear often relapses after extinction, suggesting that extinction training generates a new memory that coexists with the original fear memory; however, the mechanisms governing the expression of competing fear and extinction memories remain unclear. We used activity-dependent neural tagging to investigate representations of fear and extinction memories in the dentate gyrus. We demonstrate that extinction training suppresses reactivation of contextual fear engram cells while activating a second ensemble, a putative extinction engram. Optogenetic inhibition of neurons that were active during extinction training increased fear after extinction training, whereas silencing neurons that were active during fear training reduced spontaneous recovery of fear. Optogenetic stimulation of fear acquisition neurons increased fear, while stimulation of extinction neurons suppressed fear and prevented spontaneous recovery. Our results indicate that the hippocampus generates a fear extinction representation and that interactions between hippocampal fear and extinction representations govern the suppression and relapse of fear after extinction.
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“Activity-tagging coupled with optogenetic inhibition suggests that threat conditioning and extinction memories exist in separate populations of neurons within the hippocampus [44]”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [44]
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“For example, fetal growth rate involves coordinated epigenetic modifications to modulate the DNA chromatin structure in the liver, skeletal muscle, adipose tissue, and hypothalamus.”
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“Other investigations with models of nutritional restriction and uteroplacental insufficiency suggest that the gestational environment influences the postnatal phenotype, which may increase susceptibility to childhood obesity through metabolic reprogramming [95].”
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Metadata
- Authors
- Lacagnina, A. F., Brockway, E. T., Crovetti, C. R., Shue, F., McCarty, M. J., Sattler, K. P., Lim, S. C., Santos, S. L., Denny, C. A., & Drew, M. R.
- Affiliations
- The University of Texas at Austin (US)
- Research Foundation For Mental Hygiene (US)
- Corresponding author
- Drew, Michael R.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2019-04-01
- Volume
- 22
- Issue
- 5
- Pages
- 753-761
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6705137
- OpenAlex
- W2935468986
- Cited by
- 311
- References
- 52
- Citations by year
- 2026: 30 · 2025: 48 · 2024: 48 · 2023: 44 · 2022: 42 · 2021: 53 · 2020: 24 · 2019: 20
- FWCI
- 20.20
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health (DP5OD017908)
- National Institute of Mental Health (F31MH111243, R01MH117426, R01MH102595, T32MH106454)
- National Eye Institute (R21EY026446)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD101402)
- 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
- fear extinction, fear memory, hippocampus, dentate gyrus, engram cells, contextual fear, spontaneous recovery, optogenetic silencing, optogenetic stimulation, memory reactivation
- MeSH terms
- Animals, Conditioning, Classical, Extinction, Psychological, Fear, Female, Male, Memory, Mice, Transgenic, Neurons, Mental Recall, Dentate Gyrus, Optogenetics
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