Engrams and circuits crucial for systems consolidation of a memory
Open accessAbstract
Episodic memories initially require rapid synaptic plasticity within the hippocampus for their formation and are gradually consolidated in neocortical networks for permanent storage. However, the engrams and circuits that support neocortical memory consolidation have thus far been unknown. We found that neocortical prefrontal memory engram cells, which are critical for remote contextual fear memory, were rapidly generated during initial learning through inputs from both the hippocampal-entorhinal cortex network and the basolateral amygdala. After their generation, the prefrontal engram cells, with support from hippocampal memory engram cells, became functionally mature with time. Whereas hippocampal engram cells gradually became silent with time, engram cells in the basolateral amygdala, which were necessary for fear memory, were maintained. Our data provide new insights into the functional reorganization of engrams and circuits underlying systems consolidation of memory.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Memory maturation follows the finding that engrams form immediately but remain 'silent' for days before becoming explicitly retrievable.
“Memory maturation follows the Kitamura et al. Kitamura et al. [2017] finding that engrams form immediately but remain 'silent' for days before becoming explicitly retrievable.”
From Human-Inspired Memory Architecture for LLM Agents (2026) · cites this paper as Kitamura et al. [2017]
Maturation requires repeated retrieval over weeks to activate.
“Maturation requires repeated retrieval over weeks to activate, and reconsolidation requires cross-session contradictions, which are both structurally absent from LongMemEval's construction.”
From Human-Inspired Memory Architecture for LLM Agents (2026) · cites this paper as Kitamura et al. [2017]
Cites
McClelland, J. L., McNaughton, B. L., & O'Reilly, R. C. (1995) · Psychological Review · doi:10.1037/0033-295x.102.3.419 · Cited by 5,256 · see citing works
Simple memory: a theory for archicortex
Marr, D. (1971) · Philosophical Transactions of the Royal Society of London. B, Biological Sciences · doi:10.1098/rstb.1971.0078 · Cited by 2,771 · see citing works
Modality-Specific Retrograde Amnesia of Fear
Kim, J. J., & Fanselow, M. S. (1992) · Science · doi:10.1126/science.1585183 · Cited by 2,483 · see citing works
Schemas and Memory Consolidation.
Tse, D., Langston, R. F., Kakeyama, M., Bethus, I., Spooner, P. A., Wood, E. R., Witter, M. P., & Morris, R. G. M. (2007) · Science · doi:10.1126/science.1135935 · Cited by 1,244 · see citing works
Bidirectional switch of the valence associated with a hippocampal contextual memory engram
Redondo, R. L., Kim, J., Arons, A. L., Ramirez, S., Liu, X., & Tonegawa, S. (2014) · Nature · doi:10.1038/nature13725 · Cited by 512 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Continual lifelong learning with neural networks: A review
Parisi, G. I., Kemker, R., Part, J. L., Kanan, C., & Wermter, S. (2019) · Neural Networks · doi:10.1016/j.neunet.2019.01.012 · Cited by 3,117 · see citing works
Memory engrams: Recalling the past and imagining the future
Josselyn, S. A., & Tonegawa, S. (2020) · Science · doi:10.1126/science.aaw4325 · Cited by 1,087 · see citing works
Self-citationPrefrontal–hippocampal interactions in episodic memory
Eichenbaum, H. (2017) · Nature Reviews Neuroscience · doi:10.1038/nrn.2017.74 · Cited by 870 · see citing works
Neurobiology of Schemas and Schema-Mediated Memory
Gilboa, A., & Marlatte, H. (2017) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2017.04.013 · Cited by 742 · see citing works
Microglial Remodeling of the Extracellular Matrix Promotes Synapse Plasticity
Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.050 · Cited by 615 · see citing works
Old brains come uncoupled in sleep: slow wave-spindle synchrony, brain atrophy, and forgetting
Helfrich, R. F., Mander, B. A., Jagust, W. J., Knight, R. T., & Walker, M. P. (2018) · Neuron · doi:10.1016/j.neuron.2017.11.020 · Cited by 497 · see citing works
Disruption of oligodendrogenesis impairs memory consolidation in adult mice
Steadman, P. E., Xia, F., Ahmed, M., Mocle, A. J., Penning, A. R. A., Geraghty, A. C., Steenland, H. W., Monje, M., Josselyn, S. A., & Frankland, P. W. (2020) · Neuron · doi:10.1016/j.neuron.2019.10.013 · Cited by 426 · see citing works
The Role of Hippocampal Replay in Memory and Planning
Ólafsdóttir, H. F., Bush, D., & Barry, C. (2018) · Current Biology · doi:10.1016/j.cub.2017.10.073 · Cited by 413 · see citing works
Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus
Khodagholy, D., Gelinas, J. N., & Buzsáki, G. (2017) · Science · doi:10.1126/science.aan6203 · Cited by 357 · see citing works
The hippocampus and related neocortical structures in memory transformation
Sekeres, M. J., Winocur, G., & Moscovitch, M. (2018) · Neuroscience Letters · doi:10.1016/j.neulet.2018.05.006 · Cited by 370 · see citing works
Meningeal γδ T cell-derived IL-17 controls synaptic plasticity and short-term memory
Ribeiro, M., Brigas, H. C., Temido-Ferreira, M., Pousinha, P. A., Regen, T., Santa, C., Coelho, J. E., Marques-Morgado, I., Valente, C. A., Omenetti, S., et al. (2019) · Science Immunology · doi:10.1126/sciimmunol.aay5199 · Cited by 335 · see citing works
Myelin plasticity: sculpting circuits in learning and memory
Xin, W., & Chan, J. R. (2020) · Nature Reviews Neuroscience · doi:10.1038/s41583-020-00379-8 · Cited by 329 · see citing works
Distinct hippocampal engrams control extinction and relapse of fear memory
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. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0361-z · Cited by 311 · see citing works
Robin, J., & Moscovitch, M. (2017) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2017.07.016 · Cited by 266 · see citing works
Fast track to the neocortex: A memory engram in the posterior parietal cortex
Brodt, S., Gais, S., Beck, J., Erb, M., Scheffler, K., & Schönauer, M. (2018) · Science · doi:10.1126/science.aau2528 · Cited by 224 · see citing works
The neurobiological foundation of memory retrieval
Frankland, P. W., Josselyn, S. A., & Köhler, S. (2019) · Nature Neuroscience · doi:10.1038/s41593-019-0493-1 · Cited by 228 · see citing works
Bienkowski, M. S., Bowman, I., Song, M. Y., Gou, L., Ard, T., Cotter, K., Zhu, M., Benavidez, N. L., Yamashita, S., Abu-Jaber, J., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0241-y · Cited by 224 · see citing works
Human memory reconsolidation: A guiding framework and critical review of the evidence.
Elsey, J. W. B., Van Ast, V. A., & Kindt, M. (2018) · Psychological Bulletin · doi:10.1037/bul0000152 · Cited by 199 · see citing works
Gilboa, A., & Moscovitch, M. (2021) · Neuron · doi:10.1016/j.neuron.2021.04.025 · Cited by 174 · see citing works
Stepwise synaptic plasticity events drive the early phase of memory consolidation
Goto, A., Bota, A., Miya, K., Wang, J., Tsukamoto, S., Jiang, X., Hirai, D., Murayama, M., Matsuda, T., McHugh, T. J., et al. (2021) · Science · doi:10.1126/science.abj9195 · Cited by 184 · see citing works
Reactivation of recall-induced neurons contributes to remote fear memory attenuation
Khalaf, O., Resch, S., Dixsaut, L., Gorden, V., Glauser, L., & Gräff, J. (2018) · Science · doi:10.1126/science.aas9875 · Cited by 146 · see citing works
de Sousa, A. F., Cowansage, K. K., Zutshi, I., Cardozo, L. M., Yoo, E. J., Leutgeb, S., & Mayford, M. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1818432116 · Cited by 138 · see citing works
Inhibitory engrams in perception and memory
Barron, H. C., Vogels, T. P., Behrens, T. E., & Ramaswami, M. (2017) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1701812114 · Cited by 147 · see citing works
Hippocampal-amygdala memory circuits govern experience-dependent observational fear
Terranova, J. I., Yokose, J., Osanai, H., Marks, W. D., Yamamoto, J., Ogawa, S. K., & Kitamura, T. (2022) · Neuron · doi:10.1016/j.neuron.2022.01.019 · Cited by 117 · see citing works
Self-citationPersistent transcriptional programmes are associated with remote memory
Chen, M. B., Jiang, X., Quake, S. R., & Südhof, T. C. (2020) · Nature · doi:10.1038/s41586-020-2905-5 · Cited by 111 · see citing works
Replay in Deep Learning: Current Approaches and Missing Biological Elements
Hayes, T. L., Krishnan, G. P., Bazhenov, M., Siegelmann, H. T., Sejnowski, T. J., & Kanan, C. (2021) · Neural Computation · doi:10.1162/neco_a_01433 · Cited by 106 · see citing works
Hippocampal Place Fields Maintain a Coherent and Flexible Map across Long Timescales
Kinsky, N. R., Sullivan, D. W., Mau, W., Hasselmo, M. E., & Eichenbaum, H. B. (2018) · Current Biology · doi:10.1016/j.cub.2018.09.037 · Cited by 105 · see citing works
Experience-dependent contextual codes in the hippocampus
Plitt, M. H., & Giocomo, L. M. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00816-6 · Cited by 101 · see citing works
Organizing memories for generalization in complementary learning systems
Sun, W., Advani, M., Spruston, N., Saxe, A., & Fitzgerald, J. E. (2023) · Nature Neuroscience · doi:10.1038/s41593-023-01382-9 · Cited by 103 · see citing works
Tuscher, J. J., Taxier, L. R., Fortress, A. M., & Frick, K. M. (2018) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2018.11.002 · Cited by 88 · see citing works
Cortical–hippocampal coupling during manifold exploration in motor cortex
Kim, J., Joshi, A., Frank, L., & Ganguly, K. (2023) · Nature · doi:10.1038/s41586-022-05533-z · Cited by 77 · see citing works
Hippocampal network oscillations at the interplay between innate anxiety and learned fear
Çalışkan, G., & Stork, O. (2019) · Psychopharmacology · doi:10.1007/s00213-018-5109-z · Cited by 72 · see citing works
The sleep benefit in episodic memory: An integrative review and a meta-analysis.
Berres, S., & Erdfelder, E. (2021) · Psychological Bulletin · doi:10.1037/bul0000350 · Cited by 74 · see citing works
In vivo ephaptic coupling allows memory network formation
Pinotsis, D. A., & Miller, E. K. (2023) · Cerebral Cortex · doi:10.1093/cercor/bhad251 · Cited by 62 · see citing works
Prefrontal feature representations drive memory recall
Yadav, N., Noble, C., Niemeyer, J. E., Terceros, A., Victor, J., Liston, C., & Rajasethupathy, P. (2022) · Nature · doi:10.1038/s41586-022-04936-2 · Cited by 61 · see citing works
Khanal, P., & Hotulainen, P. (2021) · Cells · doi:10.3390/cells10092392 · Cited by 60 · see citing works
de Almeida-Filho, D. G., Koike, B. D. V., Billwiller, F., Farias, K. S., de Sales, I. R. P., Luppi, P.-H., Ribeiro, S., & Queiroz, C. M. (2021) · Scientific Reports · doi:10.1038/s41598-021-91659-5 · Cited by 56 · see citing works
Schematic memories develop quickly, but are not expressed unless necessary
Tompary, A., Zhou, W., & Davachi, L. (2020) · Scientific Reports · doi:10.1038/s41598-020-73952-x · Cited by 53 · see citing works
Laque, A., L. De Ness, G., Wagner, G. E., Nedelescu, H., Carroll, A., Watry, D., M. Kerr, T., Koya, E., Hope, B. T., Weiss, F., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11799-1 · Cited by 43 · see citing works
Memories off the top of your head
Shin, J. N., Doron, G., & Larkum, M. E. (2021) · Science · doi:10.1126/science.abk1859 · Cited by 40 · see citing works
Selective engram coreactivation in idling brain inspires implicit learning
Aly, M. H., Abdou, K., Okubo-Suzuki, R., Nomoto, M., & Inokuchi, K. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2201578119 · Cited by 39 · see citing works
Memory corticalization triggered by REM sleep: mechanisms of cellular and systems consolidation
Almeida-Filho, D. G., Queiroz, C. M., & Ribeiro, S. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-018-2886-9 · Cited by 38 · see citing works
Sleep-dependent oscillatory synchronization: A role in fear memory consolidation
Totty, M. S., Chesney, L. A., Geist, P. A., & Datta, S. (2017) · Frontiers in Neural Circuits · doi:10.3389/fncir.2017.00049 · Cited by 29 · see citing works
The generative grammar of the brain: a critique of internally generated representations
Dragoi, G. (2024) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00763-0 · Cited by 28 · see citing works
Moscovitch, M., & Gilboa, A. (2022) · Faculty Reviews · doi:10.12703/r/11-33 · Cited by 27 · see citing works
Watanabe, K., Masaoka, Y., Kawamura, M., Yoshida, M., Koiwa, N., Yoshikawa, A., Kubota, S., Ida, M., Ono, K., & Izumizaki, M. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.00687 · Cited by 21 · see citing works
Making Memories: Why Time Matters
Kelley, P., Evans, M. D. R., & Kelley, J. (2018) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2018.00400 · Cited by 10 · see citing works
Elements of episodic memory: insights from artificial agents
Boyle, A., & Blomkvist, A. (2024) · Philosophical Transactions of the Royal Society B: Biological Sciences · doi:10.1098/rstb.2023.0416 · Cited by 6 · see citing works
Role of the hippocampus in systems consolidation of remote fear memory
Park, H., & Kaang, B.-K. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01680-9 · Cited by 1 · see citing works
Nested Learning: The Illusion of Deep Learning Architectures
Behrouz, A., Razaviyayn, M., Zhong, P., & Mirrokni, V. (2025) · arXiv · doi:10.48550/arxiv.2512.24695 · Cited by 1 · see citing works
Human-Inspired Memory Architecture for LLM Agents
Kerestecioglu, D., Robsky, A., Vasters, C., Sharma, A., & Kesselman, Y. (2026) · arXiv · doi:10.48550/arxiv.2605.08538
“Memory maturation follows the Kitamura et al. Kitamura et al. [2017] finding that engrams form immediately but remain “silent” for days before becoming explicitly retrievable.”
- Authors
- Kitamura, T., Ogawa, S. K., Roy, D. S., Okuyama, T., Morrissey, M. D., Smith, L. M., Redondo, R. L., & Tonegawa, S.
- Affiliations
- RIKEN-MIT Center for Neural Circuit Genetics at the Picower Institute for Learning and Memory, Departments of Biology and Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
- Massachusetts Institute of Technology (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Tonegawa, Susumu
- ORCID
- Venue
- Science
- Published
- 2017-04-07
- Volume
- 356
- Issue
- 6333
- Pages
- 73-78
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC5493329
- OpenAlex
- W2604988916
- Cited by
- 1,104
- References
- 5
- Citations by year
- 2026: 79 · 2025: 123 · 2024: 150 · 2023: 136 · 2022: 106 · 2021: 107 · 2020: 128 · 2019: 108 · 2018: 122 · 2017: 42 · 2016: 1 · 2012: 1
- FWCI
- 62.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- PMC
- Funders
- Howard Hughes Medical Institute (award304794)
- JPB Foundation (award304797)
- RIKEN (award304795)
- 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
- memory engrams, systems consolidation, basolateral amygdala, contextual fear memory, entorhinal cortex
- MeSH terms
- Memory Consolidation, Amygdala, Animals, Conditioning, Psychological, Fear, Hippocampus, Male, Mice, Inbred C57BL, Mice, Transgenic, Neural Pathways, Neuronal Plasticity, Prefrontal Cortex, Entorhinal Cortex, Mice, Memory, Episodic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
