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Persistent transcriptional programmes are associated with remote memory
Open accessAbstract
The role of gene expression during learning and in short-term memories has been studied extensively 1-3, but less is known about remote memories, which can persist for a lifetime 4. Here we used long-term contextual fear memory as a paradigm to probe the single-cell gene expression landscape that underlies remote memory storage in the medial prefrontal cortex. We found persistent activity-specific transcriptional alterations in diverse populations of neurons that lasted for weeks after fear learning. Out of a vast plasticity-coding space, we identified genes associated with membrane fusion that could have important roles in the maintenance of remote memory. Unexpectedly, astrocytes and microglia also acquired persistent gene expression signatures that were associated with remote memory, suggesting that they actively contribute to memory circuits. The discovery of gene expression programmes associated with remote memory engrams adds an important dimension of activity-dependent cellular states to existing brain taxonomy atlases and sheds light on the elusive mechanisms of remote memory storage.
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“Threat conditioning and threat recall are associated with unique, cell-type-specific transcriptional changes that persist for weeks after initial training [57].”
From Prefrontal cortex, amygdala, and threat processing: implications for PTSD (2022) · cites this paper as [57]
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Metadata
- Authors
- Chen, M. B., Jiang, X., Quake, S. R., & Südhof, T. C.
- Affiliations
- Stanford University (US)
- Howard Hughes Medical Institute (US)
- Chan Zuckerberg Initiative (United States) (US)
- Corresponding author
- Quake, Stephen R.
- Südhof, Thomas C.
- Venue
- Nature
- Published
- 2020-11-11
- Volume
- 587
- Issue
- 7834
- Pages
- 437-442
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9097329
- OpenAlex
- W3102239735
- Cited by
- 111
- References
- 27
- Citations by year
- 2026: 13 · 2025: 18 · 2024: 26 · 2023: 21 · 2022: 17 · 2021: 15 · 2020: 1
- FWCI
- 7.26
- Type
- journal article
- Language
- en
- Update notices
- correction (2025-08-06)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- National Institutes of Health (MH115999)
- National Institute of Mental Health (R01MH115999)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- remote memory, long-term memory storage, contextual fear memory, memory engrams, transcriptional programs, single-cell gene expression, medial prefrontal cortex, astrocytes, microglia, activity-dependent gene expression
- MeSH terms
- Memory Consolidation, Animals, Astrocytes, Exocytosis, Fear, Gene Expression Regulation, Male, Neurons, Time Factors, Transcription, Genetic, Biomarkers, Prefrontal Cortex, Microglia, Mice, Memory, Long-Term, Single-Cell Analysis
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