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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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Integrating single-cell transcriptomic data across different conditions, technologies, and species
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., & Satija, R. (2018) · Nature Biotechnology · doi:10.1038/nbt.4096 · Cited by 13,174
Full-length RNA-seq from single cells using Smart-seq2
Picelli, S., Faridani, O. R., Björklund, Å. K., Winberg, G., Sagasser, S., & Sandberg, R. (2014) · Nature Protocols · doi:10.1038/nprot.2014.006 · Cited by 4,137
The molecular biology of memory storage: a dialogue between genes and synapses
Kandel, E. R. (2001) · Science · doi:10.1126/science.1067020 · Cited by 3,917
Cell types in the mouse cortex and hippocampus revealed by single-cell RNA-seq
Zeisel, A., Muñoz-Manchado, A. B., Codeluppi, S., Lönnerberg, P., La Manno, G., Juréus, A., Marques, S., Munguba, H., He, L., Betsholtz, C., et al. (2015) · Science · doi:10.1126/science.aaa1934 · Cited by 3,124
Brain energy metabolism: focus on Astrocyte-neuron metabolic cooperation
Bélanger, M., Allaman, I., & Magistretti, P. J. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.08.016 · Cited by 2,313
Molecular diversity and specializations among the cells of the adult mouse brain
Saunders, A., Macosko, E. Z., Wysoker, A., Goldman, M., Krienen, F. M., de Rivera, H., Bien, E., Baum, M., Bortolin, L., Wang, S., et al. (2018) · Cell · doi:10.1016/j.cell.2018.07.028 · Cited by 1,531
Squire, L. R. (1986) · Science · doi:10.1126/science.3086978 · Cited by 1,278
Engrams and circuits crucial for systems consolidation of a memory
Kitamura, T., Ogawa, S. K., Roy, D. S., Okuyama, T., Morrissey, M. D., Smith, L. M., Redondo, R. L., & Tonegawa, S. (2017) · Science · doi:10.1126/science.aam6808 · Cited by 1,104
A draft network of ligand–receptor-mediated multicellular signalling in human
Ramilowski, J. A., Goldberg, T., Harshbarger, J., Kloppmann, E., Lizio, M., Satagopam, V. P., Itoh, M., Kawaji, H., Carninci, P., Rost, B., et al. (2015) · Nature Communications · doi:10.1038/ncomms8866 · Cited by 887
Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits
Südhof, T. C. (2017) · Cell · doi:10.1016/j.cell.2017.10.024 · Cited by 810
Self-citationGuenthner, C. J., Miyamichi, K., Yang, H. H., Heller, H. C., & Luo, L. (2013) · Neuron · doi:10.1016/j.neuron.2013.03.025 · Cited by 705
Temporal evolution of cortical ensembles promoting remote memory retrieval
DeNardo, L. A., Liu, C. D., Allen, W. E., Adams, E. L., Friedmann, D., Dadgar‐Kiani, E., Fu, L., Guenthner, C. J., Lee, J. H., Tessier‐Lavigne, M., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0318-7 · Cited by 646
CREB required for the stability of new and reactivated fear memories
Kida, S., Josselyn, S. A., de Ortı́z, S. P., Kogan, J. H., Chévere-Torres, I., Masushige, S., & Silva, A. J. (2002) · Nature Neuroscience · doi:10.1038/nn819 · Cited by 642
Single-cell analysis of experience-dependent transcriptomic states in the mouse visual cortex
Hrvatin, S., Hochbaum, D. R., Nagy, M. A., Cicconet, M., Robertson, K., Cheadle, L., Zilionis, R., Ratner, A., Borges-Monroy, R., Klein, A. M., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-017-0029-5 · Cited by 497
Nuclear RNA-seq of single neurons reveals molecular signatures of activation
Lacar, B., Linker, S. B., Jaeger, B. N., Krishnaswami, S. R., Barron, J. J., Kelder, M. J. E., Parylak, S. L., Paquola, A. C. M., Venepally, P., Novotny, M., et al. (2016) · Nature Communications · doi:10.1038/ncomms11022 · Cited by 405
Consolidation and Reconsolidation: Two Lives of Memories?
McKenzie, S., & Eichenbaum, H. (2011) · Neuron · doi:10.1016/j.neuron.2011.06.037 · Cited by 368
The Regulation of Transcription in Memory Consolidation
Alberini, C. M., & Kandel, E. R. (2015) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a021741 · Cited by 362
Microglia and Memory: Modulation by Early-Life Infection
Williamson, L. L., Sholar, P. W., Mistry, R. S., Smith, S. H., & Bilbo, S. D. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3688-11.2011 · Cited by 274
Upregulation of CREB-Mediated Transcription Enhances Both Short- and Long-Term Memory
Suzuki, A., Fukushima, H., Mukawa, T., Toyoda, H., Wu, L.-J., Zhao, M.-G., Xu, H., Shang, Y., Endoh, K., Iwamoto, T., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3257-10.2011 · Cited by 250
Serinc, an activity-regulated protein family, incorporates serine into membrane lipid synthesis
Inuzuka, M., Hayakawa, M., & Ingi, T. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m505712200 · Cited by 198
Mechanism of phospholipid binding by the C2A-domain of synaptotagmin I.
Zhang, X., Rizo, J., & Südhof, T. (1998) · Biochemistry · doi:10.1021/bi9807512 · Cited by 190
Self-citationGenetic strategies to access activated neurons
DeNardo, L. A., & Luo, L. (2017) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2017.05.014 · Cited by 148
Engram-specific transcriptome profiling of contextual memory consolidation
Rao‐Ruiz, P., Couey, J. J., Marcelo, I. M., Bouwkamp, C. G., Slump, D. E., Matos, M. R., van der Loo, R. J., Martins, G. J., van den Hout, M. C. G. N., van IJcken, W. F. J., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09960-x · Cited by 146
Flexner, L. B., & Flexner, J. B. (1966) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.55.2.369 · Cited by 114
Zhou, M., Liu, Z., Melin, M. D., Ng, Y. H., Xu, W., & Südhof, T. C. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0248-4 · Cited by 112
Self-citationCho, J.-H., Huang, B. S., & Gray, J. M. (2016) · Scientific Reports · doi:10.1038/srep31753 · Cited by 33
(2012) · BENTHAM SCIENCE PUBLISHERS eBooks · doi:10.2174/978160805257811201010043 · Cited by 4
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Sun, W., Liu, Z., Jiang, X., Chen, M. B., Dong, H., Liu, J., Südhof, T. C., & Quake, S. R. (2024) · Nature · doi:10.1038/s41586-023-07011-6 · Cited by 165
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Chiareli, R. A., Carvalho, G. A., Marques, B. L., Mota, L. S., Oliveira‐Lima, O. C., Gomes, R. M., Birbrair, A., Gomez, R. S., Simão, F., Klempin, F., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.665795 · Cited by 130
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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