McClelland, J. L., McNaughton, B. L. & O’Reilly, R. C. Why there are complementary learning systems in the hippocampus and neocortex: insights from the successes and failures of connectionist models of learning and memory. Psychol. Rev. 102, 419 (1995).
Shepard, R. N. Toward a universal law of generalization for psychological science. Science 237, 1317–1323 (1987).
Richards, B. A. & Frankland, P. W. The persistence and transience of memory. Neuron 94, 1071–1084 (2017).
Nadel, L. & Moscovitch, M. Memory consolidation, retrograde amnesia and the hippocampal complex. Curr. Opin. Neurobiol. 7, 217–227 (1997).
Tulving, E. Episodic memory: from mind to brain. Annu. Rev. Psychol. 53, 1–25 (2002).
Winocur, G. & Moscovitch, M. Memory transformation and systems consolidation. J. Int. Neuropsychol. Soc. 17, 766–780 (2011).
Moscovitch, M., Cabeza, R., Winocur, G. & Nadel, L. Episodic memory and beyond: the hippocampus and neocortex in transformation. Annu. Rev. Psychol. 67, 105–134 (2016).
Tonegawa, S., Morrissey, M. D. & Kitamura, T. The role of engram cells in the systems consolidation of memory. Nat. Rev. Neurosci. 19, 485–498 (2018).
Barry, D. N. & Maguire, E. A. Remote memory and the hippocampus: a constructive critique. Trends Cogn. Sci. 23, 128–142 (2019).
Gilboa, A. & Moscovitch, M. No consolidation without representation: correspondence between neural and psychological representations in recent and remote memory. Neuron 109, 2239–2255 (2021).
Buckner, R. L. The role of the hippocampus in prediction and imagination. Annu. Review Psychol. 61, 27–48 (2010).
Brown, T. I. et al. Prospective representation of navigational goals in the human hippocampus. Science 352, 1323–1326 (2016).
Garvert, M. M., Saanum, T., Schulz, E., Schuck, N. W. & Doeller, C. F. Hippocampal spatio-predictive cognitive maps adaptively guide reward generalization. Nat. Neurosci. 26, 615–626 (2023).
Courellis, H. S. et al. Abstract representations emerge in human hippocampal neurons during inference. Nature 632, 841–849 (2024).
Hassabis, D., Kumaran, D., Vann, S. D. & Maguire, E. A. Patients with hippocampal amnesia cannot imagine new experiences. Proc. Natl Acad. Sci. USA 104, 1726–1731 (2007).
Hassabis, D. & Maguire, E. A. Deconstructing episodic memory with construction. Trends Cogn. Sci. 11, 299–306 (2007).
Spens, E. & Burgess, N. A generative model of memory construction and consolidation. Nat. Hum. Behav. 8, 526–543 (2024).
Allen, T. A. & Fortin, N. J. The evolution of episodic memory. Proc. Natl Acad. Sci. USA 110, 10379–10386 (2013).
Winocur, G., Moscovitch, M. & Sekeres, M. Memory consolidation or transformation: context manipulation and hippocampal representations of memory. Nat. Neurosci. 10, 555–557 (2007).
Wiltgen, B. J. & Silva, A. J. Memory for context becomes less specific with time. Learn. Mem. 14, 313–317 (2007).
DeNardo, L. A. et al. Temporal evolution of cortical ensembles promoting remote memory retrieval. Nat. Neurosci. 22, 460–469 (2019).
Kitamura, T. et al. Engrams and circuits crucial for systems consolidation of a memory. Science 356, 73–78 (2017).
Guskjolen, A. et al. Recovery of “lost” infant memories in mice. Curr. Biol. 28, 2283–2290 (2018).
Broussard, G. J. et al. In vivo measurement of afferent activity with axon-specific calcium imaging. Nat. Neurosci. 21, 1272–1280 (2018).
Mocle, A. J. et al. Excitability mediates allocation of pre-configured ensembles to a hippocampal engram supporting contextual conditioned threat in mice. Neuron 112, 1487–1497 (2024).
Mahn, M. et al. Efficient optogenetic silencing of neurotransmitter release with a mosquito rhodopsin. Neuron 109, 1621–1635 (2021).
Tse, D. et al. Schemas and memory consolidation. Science 316, 76–82 (2007).
Tse, D. et al. Schema-dependent gene activation and memory encoding in neocortex. Science 333, 891–895 (2011).
Atucha, E., Ku, S.-P., Lippert, M. T. & Sauvage, M. M. Recalling gist memory depends on CA1 hippocampal neurons for lifetime retention and CA3 neurons for memory precision. Cell Rep. 42, 113317 (2023).
Choi, J.-H. et al. Interregional synaptic maps among engram cells underlie memory formation. Science 360, 430–435 (2018).
Ruediger, S. et al. Learning-related feedforward inhibitory connectivity growth required for memory precision. Nature 473, 514–518 (2011).
Guo, N. et al. Dentate granule cell recruitment of feedforward inhibition governs engram maintenance and remote memory generalization. Nat. Med. 24, 438–449 (2018).
Chklovskii, D. B., Mel, B. & Svoboda, K. Cortical rewiring and information storage. Nature 431, 782–788 (2004).
Govindarajan, A., Kelleher, R. J. & Tonegawa, S. A clustered plasticity model of long-term memory engrams. Nat. Rev. Neurosci. 7, 575–583 (2006).
Lee, C. & Kaang, B.-K. Clustering of synaptic engram: functional and structural basis of memory. Neurobiol. Learn. Mem. 216, 107993 (2024).
Kitamura, T. et al. Adult neurogenesis modulates the hippocampus-dependent period of associative fear memory. Cell 139, 814–827 (2009).
Zhao, C., Teng, E. M., Summers, R. G., Ming, G.-l & Gage, F. H. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J. Neurosci. 26, 3–11 (2006).
Toni, N. et al. Synapse formation on neurons born in the adult hippocampus. Nat. Neurosci. 10, 727–734 (2007).
Ge, S., Yang, C.-h, Hsu, K.-s, Ming, G.-l & Song, H. A critical period for enhanced synaptic plasticity in newly generated neurons of the adult brain. Neuron 54, 559–566 (2007).
Marín-Burgin, A., Mongiat, L. A., Pardi, M. B. & Schinder, A. F. Unique processing during a period of high excitation/inhibition balance in adult-born neurons. Science 335, 1238–1242 (2012).
Gu, Y. et al. Optical controlling reveals time-dependent roles for adult-born dentate granule cells. Nat. Neurosci. 15, 1700–1706 (2012).
Denoth-Lippuner, A. & Jessberger, S. Formation and integration of new neurons in the adult hippocampus. Nat. Rev. Neurosci. 22, 223–236 (2021).
Toni, N. et al. Neurons born in the adult dentate gyrus form functional synapses with target cells. Nat. Neurosci. 11, 901–907 (2008).
Monje, M. L., Mizumatsu, S., Fike, J. R. & Palmer, T. D. Irradiation induces neural precursor-cell dysfunction. Nat. Med. 8, 955–962 (2002).
Van Praag, H., Kempermann, G. & Gage, F. H. Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat. Neurosci. 2, 266–270 (1999).
Guskjolen, A. et al. Neurogenesis-mediated circuit remodeling reduces engram reinstatement and promotes forgetting. Preprint at bioRxiv https://doi.org/10.1101/2023.10.10.561722 (2023).
Williams, M. E. et al. Cadherin-9 regulates synapse-specific differentiation in the developing hippocampus. Neuron 71, 640–655 (2011).
Frankland, P. W. & Bontempi, B. The organization of recent and remote memories. Nat. Rev. Neurosci. 6, 119–130 (2005).
Squire, L. R. & Alvarez, P. Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr. Opin. Neurobiol. 5, 169–177 (1995).
Ko, S. Y. & Frankland, P. W. Neurogenesis-dependent transformation of hippocampal engrams. Neurosci. Lett. 762, 136176 (2021).
Akers, K. G. et al. Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344, 598–602 (2014).
Ziv, Y. et al. Long-term dynamics of CA1 hippocampal place codes. Nat. Neurosci. 16, 264–266 (2013).
Miller, A. M. et al. Emergence of a predictive model in the hippocampus. Neuron 111, 1952–1965 (2023).
Hindy, N. C., Ng, F. Y. & Turk-Browne, N. B. Linking pattern completion in the hippocampus to predictive coding in visual cortex. Nat. Neurosci. 19, 665–667 (2016).
Barron, H. C., Auksztulewicz, R. & Friston, K. Prediction and memory: a predictive coding account. Prog. Neurobiol. 192, 101821 (2020).
Kumar, D. et al. Sparse activity of hippocampal adult-born neurons during REM sleep is necessary for memory consolidation. Neuron 107, 552–565 (2020).
Josselyn, S. A. & Tonegawa, S. Memory engrams: recalling the past and imagining the future. Science 367, eaaw4325 (2020).
Sahay, A. et al. Increasing adult hippocampal neurogenesis is sufficient to improve pattern separation. Nature 472, 466–470 (2011).
Kumaran, D. & McClelland, J. L. Generalization through the recurrent interaction of episodic memories: a model of the hippocampal system. Psychol. Rev. 119, 573 (2012).
Van Kesteren, M. T. et al. Differential roles for medial prefrontal and medial temporal cortices in schema-dependent encoding: from congruent to incongruent. Neuropsychologia 51, 2352–2359 (2013).
Lei, B. et al. Reconstructing a new hippocampal engram for systems reconsolidation and remote memory updating. Neuron 113, 471–485 (2024).
Imayoshi, I., Ohtsuka, T., Metzger, D., Chambon, P. & Kageyama, R. Temporal regulation of Cre recombinase activity in neural stem cells. Genesis 44, 233–238 (2006).
Imayoshi, I. et al. Roles of continuous neurogenesis in the structural and functional integrity of the adult forebrain. Nat. Neurosci. 11, 1153–1161 (2008).
Sun, M. Y., Yetman, M. J., Lee, T. C., Chen, Y. & Jankowsky, J. L. Specificity and efficiency of reporter expression in adult neural progenitors vary substantially among nestin‐CreERT2 lines. J. Comp. Neurol. 522, 1191–1208 (2014).
Duan, Y. et al. Semaphorin 5 A inhibits synaptogenesis in early postnatal-and adult-born hippocampal dentate granule cells. eLife 3, e04390 (2014).
Wang, S.-H., Teixeira, C. M., Wheeler, A. L. & Frankland, P. W. The precision of remote context memories does not require the hippocampus. Nat. Neurosci. 12, 253–255 (2009).
Kee, N., Teixeira, C. M., Wang, A. H. & Frankland, P. W. Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat. Neurosci. 10, 355–362 (2007).
Maei, H. R., Zaslavsky, K., Teixeira, C. M. & Frankland, P. W. What is the most sensitive measure of water maze probe test performance? Front. Integr. Neurosci. 3, 493 (2009).
Maei, H. R. et al. Development and validation of a sensitive entropy-based measure for the water maze. Front. Integr. Neurosci. 3, 870 (2009).
Richards, B. A. et al. Patterns across multiple memories are identified over time. Nat. Neurosci. 17, 981–986 (2014).
Berndt, A. et al. Structural foundations of optogenetics: determinants of channelrhodopsin ion selectivity. Proc. Natl Acad. Sci. USA 113, 822–829 (2016).
Tashiro, A., Zhao, C. & Gage, F. H. Retrovirus-mediated single-cell gene knockout technique in adult newborn neurons in vivo. Nat. Protoc. 1, 3049–3055 (2006).
Paxinos, G. & Franklin, K. B. Paxinos and Franklin’s the Mouse Brain in Stereotaxic Coordinates (Academic, 2019).
Guenthner, C. J., Miyamichi, K., Yang, H. H., Heller, H. C. & Luo, L. Permanent genetic access to transiently active neurons via TRAP: targeted recombination in active populations. Neuron 78, 773–784 (2013).
Mathis, A. et al. DeepLabCut: markerless pose estimation of user-defined body parts with deep learning. Nat. Neurosci. 21, 1281–1289 (2018).
Sherathiya, V. N., Schaid, M. D., Seiler, J. L., Lopez, G. C. & Lerner, T. N. GuPPy, a Python toolbox for the analysis of fiber photometry data. Sci. Rep. 11, 24212 (2021).
Kim, J. et al. mGRASP enables mapping mammalian synaptic connectivity with light microscopy. Nat. Methods 9, 96–102 (2012).
Druckmann, S. et al. Structured synaptic connectivity between hippocampal regions. Neuron 81, 629–640 (2014).
Chehrehasa, F., Meedeniya, A. C., Dwyer, P., Abrahamsen, G. & Mackay-Sim, A. EdU, a new thymidine analogue for labelling proliferating cells in the nervous system. J. Neurosci. Methods 177, 122–130 (2009).
Zeng, C. et al. Evaluation of 5-ethynyl-2′-deoxyuridine staining as a sensitive and reliable method for studying cell proliferation in the adult nervous system. Brain Res. 1319, 21–32 (2010).
Fujikawa, R. et al. Neurogenesis-dependent remodeling of hippocampal circuits reduces PTSD-like behaviors in adult mice. Mol. Psychiatry 29, 3316–3329 (2024).
Lagace, D. C. et al. Dynamic contribution of nestin-expressing stem cells to adult neurogenesis. J. Neurosci. 27, 12623–12629 (2007).
Arruda-Carvalho, M., Sakaguchi, M., Akers, K. G., Josselyn, S. A. & Frankland, P. W. Posttraining ablation of adult-generated neurons degrades previously acquired memories. J. Neurosci. 31, 15113–15127 (2011).
Ramsaran, A. I. et al. A shift in the mechanisms controlling hippocampal engram formation during brain maturation. Science 380, 543–551 (2023).
Ko, S. et al. Systems consolidation reorganizes hippocampal engram circuitry – source data. Zenodo https://doi.org/10.5281/zenodo.14713972 (2025).
