Engram mechanisms of memory linking and identity (original) (raw)

• Semon, R. W. The Mneme (Allen & Unwin, 1921).
• Hebb, D. O. The Organization of Behavior: A Neuropsychological Theory (Wiley, 1949).
• Rasmussen, W. P. A. T. The Cerebral Cortex of Man; A Clinical Study of Localization of Function (Macmillan, 1950).
• Scoville, W. B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Neurosurg. Psychiatry 20, 11–21 (1957).
  Article CAS PubMed PubMed Central Google Scholar
• Reijmers, L. G., Perkins, B. L., Matsuo, N. & Mayford, M. Localization of a stable neural correlate of associative memory. Science 317, 1230–1233 (2007).
  Article CAS PubMed Google Scholar
• Han, J. H. et al. Selective erasure of a fear memory. Science 323, 1492–1496 (2009).
  Article CAS PubMed Google Scholar
• Liu, X. et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484, 381–385 (2012). This seminal study demonstrates the sufficiency of specific engram cells for memory recall.
  Article CAS PubMed PubMed Central Google Scholar
• Ramirez, S. et al. Creating a false memory in the hippocampus. Science 341, 387–391 (2013).
  Article CAS PubMed Google Scholar
• Ohkawa, N. et al. Artificial association of pre-stored information to generate a qualitatively new memory. Cell Rep. 11, 261–269 (2015). This study uses the co-reactivation of distinct engrams as a mechanism for memory linking.
  Article CAS PubMed Google Scholar
• Cowansage, K. K. et al. Direct reactivation of a coherent neocortical memory of context. Neuron 84, 432–441 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Ghandour, K. et al. Orchestrated ensemble activities constitute a hippocampal memory engram. Nat. Commun. 10, 2637 (2019).
  Article PubMed PubMed Central Google Scholar
• Koya, E. et al. Targeted disruption of cocaine-activated nucleus accumbens neurons prevents context-specific sensitization. Nat. Neurosci. 12, 1069–1073 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Park, A. et al. Formation and fate of an engram in the lateral amygdala supporting a rewarding memory in mice. Neuropsychopharmacology 48, 724–733 (2023).
  Article PubMed Google Scholar
• Roy, D. S. et al. Brain-wide mapping reveals that engrams for a single memory are distributed across multiple brain regions. Nat. Commun. 13, 1799 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Tanaka, K. Z. et al. The hippocampal engram maps experience but not place. Science 361, 392–397 (2018).
  Article CAS PubMed Google Scholar
• Josselyn, S. A. & Tonegawa, S. Memory engrams: recalling the past and imagining the future. Science 367, eaaw4325 (2020). This work comprehensively reviews memory engrams.
  Article CAS PubMed PubMed Central Google Scholar
• Tonegawa, S., Liu, X., Ramirez, S. & Redondo, R. Memory engram cells have come of age. Neuron 87, 918–931 (2015).
  Article CAS PubMed Google Scholar
• Hayashi-Takagi, A. et al. Labelling and optical erasure of synaptic memory traces in the motor cortex. Nature 525, 333–338 (2015). This pioneering study demonstrates how specific synapses regulate memories by developing synaptic optogenetics.
  Article CAS PubMed PubMed Central Google Scholar
• Lee, C. et al. Hippocampal engram networks for fear memory recruit new synapses and modify pre-existing synapses in vivo. Curr. Biol. 33, 507–516.e3 (2023).
  Article CAS PubMed Google Scholar
• Lee, J. H., Kim, W. B., Park, E. H. & Cho, J. H. Neocortical synaptic engrams for remote contextual memories. Nat. Neurosci. 26, 259–273 (2023).
  Article CAS PubMed Google Scholar
• Choi, D. I. et al. Synaptic correlates of associative fear memory in the lateral amygdala. Neuron 109, 2717–2726.e3 (2021).
  Article CAS PubMed Google Scholar
• Cai, D. J. et al. A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534, 115–118 (2016). This study provides the basis for prospective linking of contextual memories.
  Article CAS PubMed PubMed Central Google Scholar
• Chowdhury, A. et al. A locus coeruleus–dorsal CA1 dopaminergic circuit modulates memory linking. Neuron 110, 3374–3388.e8 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Rashid, A. J. et al. Competition between engrams influences fear memory formation and recall. Science 353, 383–387 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Zeithamova, D. & Preston, A. R. Temporal proximity promotes integration of overlapping events. J. Cogn. Neurosci. 29, 1311–1323 (2017).
  Article PubMed PubMed Central Google Scholar
• Aly, M. H., Abdou, K., Okubo-Suzuki, R., Nomoto, M. & Inokuchi, K. Selective engram coreactivation in idling brain inspires implicit learning. Proc. Natl Acad. Sci. 119, e2201578119 (2022). This study demonstrates retrospective linking of contextual memories through offline co-reactivation.
  Article CAS PubMed PubMed Central Google Scholar
• Barron, H. C. et al. Neuronal computation underlying inferential reasoning in humans and mice. Cell 183, 228–243.e21 (2020).
  Article CAS PubMed PubMed Central Google Scholar
• Yokose, J. et al. Overlapping memory trace indispensable for linking, but not recalling, individual memories. Science 355, 398–403 (2017). This study unveils the function of overlapping engram ensembles.
  Article CAS PubMed Google Scholar
• Shen, Y. et al. CCR5 closes the temporal window for memory linking. Nature 606, 146–152 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Nomoto, M. et al. Cellular tagging as a neural network mechanism for behavioural tagging. Nat. Commun. 7, 12319 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Abdou, K. et al. Synapse-specific representation of the identity of overlapping memory engrams. Science 360, 1227–1231 (2018). This study demonstrates how memories stored in the same neuron may have different fates.
  Article CAS PubMed Google Scholar
• Nabavi, S. et al. Engineering a memory with LTD and LTP. Nature 511, 348–352 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Yang, G. et al. Sleep promotes branch-specific formation of dendritic spines after learning. Science 344, 1173–1178 (2014). In addition to the role of sleep in spine formation, this study reveals the branch specificity of dendritic allocation.
  Article CAS PubMed PubMed Central Google Scholar
• Sehgal, M. et al. Co-allocation to overlapping dendritic branches in the retrosplenial cortex integrates memories across time. Preprint at bioRxiv https://doi.org/10.1101/2021.10.28.466343 (2021).
• Legenstein, R. & Maass, W. Branch-specific plasticity enables self-organization of nonlinear computation in single neurons. J. Neurosci. 31, 10787–10802 (2011). This paper provides powerful computational evidence of the merits of dendritic non-linearities in enhancing neuronal computation.
  Article CAS PubMed PubMed Central Google Scholar
• Kastellakis, G., Tasciotti, S., Pandi, I. & Poirazi, P. The dendritic engram. Front. Behav. Neurosci. 17, 1212139 (2023). This work comprehensively reviews dendritic non-linearities and their contribution to memory engrams.
  Article CAS PubMed PubMed Central Google Scholar
• Clark, R. E. The classical origins of Pavlov’s conditioning. Integr. Physiol. Behav. Sci. 39, 279–294 (2004).
  Article PubMed Google Scholar
• Guzowski, J. F., McNaughton, B. L., Barnes, C. A. & Worley, P. F. Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nat. Neurosci. 2, 1120–1124 (1999).
  Article CAS PubMed Google Scholar
• Barot, S. K., Chung, A., Kim, J. J. & Bernstein, I. L. Functional imaging of stimulus convergence in amygdalar neurons during Pavlovian fear conditioning. PLoS ONE 4, e6156 (2009).
  Article PubMed PubMed Central Google Scholar
• Barot, S. K., Kyono, Y., Clark, E. W. & Bernstein, I. L. Visualizing stimulus convergence in amygdala neurons during associative learning. Proc. Natl Acad. Sci. USA 105, 20959–20963 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Chung, A., Barot, S. K., Kim, J. J. & Bernstein, I. L. Biologically predisposed learning and selective associations in amygdalar neurons. Learn. Mem. 18, 371–374 (2011).
  Article PubMed PubMed Central Google Scholar
• Hashikawa, K. et al. Blockade of stimulus convergence in amygdala neurons disrupts taste associative learning. J. Neurosci. 33, 4958–4963 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Grewe, B. F. et al. Neural ensemble dynamics underlying a long-term associative memory. Nature 543, 670–675 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Nomoto, M. et al. Hippocampus as a sorter and reverberatory integrator of sensory inputs. Nat. Commun. 13, 7413 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Suzuki, A. et al. A cortical cell ensemble in the posterior parietal cortex controls past experience-dependent memory updating. Nat. Commun. 13, 41 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Ballarini, F., Moncada, D., Martinez, M. C., Alen, N. & Viola, H. Behavioral tagging is a general mechanism of long-term memory formation. Proc. Natl Acad. Sci. USA 106, 14599–14604 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Gastaldi, C., Schwalger, T., De Falco, E., Quiroga, R. Q. & Gerstner, W. When shared concept cells support associations: theory of overlapping memory engrams. PLoS Comput. Biol. 17, e1009691 (2021). This modelling study exemplifies the dynamic nature of engram overlap and memory linking.
  Article CAS PubMed PubMed Central Google Scholar
• Chandran, M. & Thorwart, A. Time in associative learning: a review on temporal maps. Front. Hum. Neurosci. 15, 617943 (2021).
  Article PubMed PubMed Central Google Scholar
• Kitamura, T. et al. Hippocampal function is not required for the precision of remote place memory. Mol. Brain 5, 5 (2012).
  Article PubMed PubMed Central Google Scholar
• Palmer, J. H. & Gong, P. Associative learning of classical conditioning as an emergent property of spatially extended spiking neural circuits with synaptic plasticity. Front. Comput. Neurosci. 8, 79 (2014).
  Article PubMed PubMed Central Google Scholar
• Arcediano, F. & Miller, R. R. Some constraints for models of timing: a temporal coding hypothesis perspective. Learn. Motiv. 33, 105–123 (2002).
  Article Google Scholar
• Nomoto, M. & Inokuchi, K. Behavioral, cellular, and synaptic tagging frameworks. Neurobiol. Learn. Mem. 153, 13–20 (2018).
  Article PubMed Google Scholar
• Moyer, J. R. Jr., Thompson, L. T. & Disterhoft, J. F. Trace eyeblink conditioning increases CA1 excitability in a transient and learning-specific manner. J. Neurosci. 16, 5536–5546 (1996).
  Article CAS PubMed Google Scholar
• Zhou, Y. et al. CREB regulates excitability and the allocation of memory to subsets of neurons in the amygdala. Nat. Neurosci. 12, 1438–1443 (2009). This work highlights neuronal excitability as a key mechanism for memory allocation.
  Article CAS PubMed PubMed Central Google Scholar
• Han, J. H. et al. Neuronal competition and selection during memory formation. Science 316, 457–460 (2007).
  Article CAS PubMed Google Scholar
• Sano, Y. et al. CREB regulates memory allocation in the insular cortex. Curr. Biol. 24, 2833–2837 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Park, S. et al. Neuronal allocation to a hippocampal engram. Neuropsychopharmacology 41, 2987–2993 (2016).
  Article CAS PubMed PubMed Central Google Scholar
• Lavi, A. et al. Local memory allocation recruits memory ensembles across brain regions. Neuron 111, 470–480.e5 (2023).
  Article CAS PubMed Google Scholar
• Lisman, J., Cooper, K., Sehgal, M. & Silva, A. J. Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability. Nat. Neurosci. 21, 309–314 (2018). This review links somatic and synaptic mechanisms for memory formation and linking.
  Article CAS PubMed PubMed Central Google Scholar
• Yiu, A. P. et al. Neurons are recruited to a memory trace based on relative neuronal excitability immediately before training. Neuron 83, 722–735 (2014).
  Article CAS PubMed Google Scholar
• Zhang, J. et al. c-fos regulates neuronal excitability and survival. Nat. Genet. 30, 416–420 (2002).
  Article CAS PubMed Google Scholar
• Tanaka, K. Z. et al. Cortical representations are reinstated by the hippocampus during memory retrieval. Neuron 84, 347–354 (2014).
  Article CAS PubMed Google Scholar
• Nakagami, Y., Watakabe, A. & Yamamori, T. Monocular inhibition reveals temporal and spatial changes in gene expression in the primary visual cortex of marmoset. Front. Neural Circuits 7, 43 (2013).
  Article PubMed PubMed Central Google Scholar
• Thompson, C. L. et al. Molecular and anatomical signatures of sleep deprivation in the mouse brain. Front. Neurosci. 4, 165 (2010).
  Article PubMed PubMed Central Google Scholar
• Chowdhury, S. et al. Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron 52, 445–459 (2006).
  Article CAS PubMed PubMed Central Google Scholar
• Plath, N. et al. Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron 52, 437–444 (2006).
  Article CAS PubMed Google Scholar
• Mizunuma, M. et al. Unbalanced excitability underlies offline reactivation of behaviorally activated neurons. Nat. Neurosci. 17, 503–505 (2014).
  Article CAS PubMed Google Scholar
• Lin, Y. et al. Activity-dependent regulation of inhibitory synapse development by Npas4. Nature 455, 1198–1204 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Spiegel, I. et al. Npas4 regulates excitatory–inhibitory balance within neural circuits through cell-type-specific gene programs. Cell 157, 1216–1229 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Ploski, J. E., Monsey, M. S., Nguyen, T., DiLeone, R. J. & Schafe, G. E. The neuronal PAS domain protein 4 (Npas4) is required for new and reactivated fear memories. PLoS ONE 6, e23760 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Sala, C. et al. Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a. J. Neurosci. 23, 6327–6337 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• Inoue, N. et al. Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation. Mol. Brain 2, 7 (2009).
  Article PubMed PubMed Central Google Scholar
• Aydin-Abidin, S., Trippe, J., Funke, K., Eysel, U. T. & Benali, A. High- and low-frequency repetitive transcranial magnetic stimulation differentially activates c-Fos and zif268 protein expression in the rat brain. Exp. Brain Res. 188, 249–261 (2008).
  Article CAS PubMed Google Scholar
• Cole, A. J., Saffen, D. W., Baraban, J. M. & Worley, P. F. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature 340, 474–476 (1989).
  Article CAS PubMed Google Scholar
• Xie, H. et al. In vivo imaging of immediate early gene expression reveals layer-specific memory traces in the mammalian brain. Proc. Natl Acad. Sci. USA 111, 2788–2793 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Kim, S., Kim, H. & Um, J. W. Synapse development organized by neuronal activity-regulated immediate-early genes. Exp. Mol. Med. 50, 1–7 (2018).
  PubMed PubMed Central Google Scholar
• Minatohara, K., Akiyoshi, M. & Okuno, H. Role of immediate-early genes in synaptic plasticity and neuronal ensembles underlying the memory trace. Front. Mol. Neurosci. 8, 78 (2015).
  PubMed Google Scholar
• Lee, J. Y. et al. Dopamine facilitates associative memory encoding in the entorhinal cortex. Nature 598, 321–326 (2021).
  Article CAS PubMed PubMed Central Google Scholar
• Han, D. H., Park, P., Choi, D. I., Bliss, T. V. P. & Kaang, B. K. The essence of the engram: cellular or synaptic? Semin. Cell Dev. Biol. 125, 122–135 (2022).
  Article CAS PubMed Google Scholar
• Yang, G., Pan, F. & Gan, W. B. Stably maintained dendritic spines are associated with lifelong memories. Nature 462, 920–924 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Xu, Z., Geron, E., Perez-Cuesta, L. M., Bai, Y. & Gan, W. B. Generalized extinction of fear memory depends on co-allocation of synaptic plasticity in dendrites. Nat. Commun. 14, 503 (2023).
  Article CAS PubMed PubMed Central Google Scholar
• Ko, B. et al. Npas4-mediated dopaminergic regulation of safety memory consolidation. Cell Rep. 42, 112678 (2023).
  Article CAS PubMed Google Scholar
• Choi, J. H. et al. Interregional synaptic maps among engram cells underlie memory formation. Science 360, 430–435 (2018).
  Article CAS PubMed Google Scholar
• Bittner, K. C., Milstein, A. D., Grienberger, C., Romani, S. & Magee, J. C. Behavioral time scale synaptic plasticity underlies CA1 place fields. Science 357, 1033–1036 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, D., Lin, B. J. & Lee, A. K. Hippocampal place fields emerge upon single-cell manipulation of excitability during behavior. Science 337, 849–853 (2012).
  Article CAS PubMed Google Scholar
• Sheffield, M. E. & Dombeck, D. A. Dendritic mechanisms of hippocampal place field formation. Curr. Opin. Neurobiol. 54, 1–11 (2019).
  Article CAS PubMed Google Scholar
• Sheffield, M. E. J., Adoff, M. D. & Dombeck, D. A. Increased prevalence of calcium transients across the dendritic arbor during place field formation. Neuron 96, 490–504.e5 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Lavzin, M., Rapoport, S., Polsky, A., Garion, L. & Schiller, J. Nonlinear dendritic processing determines angular tuning of barrel cortex neurons in vivo. Nature 490, 397–401 (2012).
  Article CAS PubMed Google Scholar
• Wilson, D. E., Whitney, D. E., Scholl, B. & Fitzpatrick, D. Orientation selectivity and the functional clustering of synaptic inputs in primary visual cortex. Nat. Neurosci. 19, 1003–1009 (2016). This work is an experimental display of how synaptic clustering and dendritic mechanisms control neuronal tuning.
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, N., Oertner, T. G., Hegemann, P. & Larkum, M. E. Active cortical dendrites modulate perception. Science 354, 1587–1590 (2016).
  Article CAS PubMed Google Scholar
• Mel, B. W. NMDA-based pattern discrimination in a modeled cortical neuron. Neural Comput. 4, 502–517 (1992).
  Article Google Scholar
• Poirazi, P. & Mel, B. W. Impact of active dendrites and structural plasticity on the memory capacity of neural tissue. Neuron 29, 779–796 (2001).
  Article CAS PubMed Google Scholar
• Poirazi, P. & Papoutsi, A. Illuminating dendritic function with computational models. Nat. Rev. Neurosci. 21, 303–321 (2020).
  Article CAS PubMed Google Scholar
• Kastellakis, G. & Poirazi, P. Synaptic clustering and memory formation. Front. Mol. Neurosci. 12, 300 (2019). This work comprehensively reviews the mechanisms, patterns and outcomes of synaptic clustering.
  Article CAS PubMed PubMed Central Google Scholar
• Rogerson, T. et al. Synaptic tagging during memory allocation. Nat. Rev. Neurosci. 15, 157–169 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Larkum, M. E. & Nevian, T. Synaptic clustering by dendritic signalling mechanisms. Curr. Opin. Neurobiol. 18, 321–331 (2008).
  Article CAS PubMed Google Scholar
• Nevian, T., Larkum, M. E., Polsky, A. & Schiller, J. Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study. Nat. Neurosci. 10, 206–214 (2007).
  Article CAS PubMed Google Scholar
• Llinas, R., Nicholson, C., Freeman, J. A. & Hillman, D. E. Dendritic spikes and their inhibition in alligator Purkinje cells. Science 160, 1132–1135 (1968).
  Article CAS PubMed Google Scholar
• Wei, D. S. et al. Compartmentalized and binary behavior of terminal dendrites in hippocampal pyramidal neurons. Science 293, 2272–2275 (2001).
  Article CAS PubMed Google Scholar
• Hausser, M., Spruston, N. & Stuart, G. J. Diversity and dynamics of dendritic signaling. Science 290, 739–744 (2000).
  Article CAS PubMed Google Scholar
• Larkum, M. E., Nevian, T., Sandler, M., Polsky, A. & Schiller, J. Synaptic integration in tuft dendrites of layer 5 pyramidal neurons: a new unifying principle. Science 325, 756–760 (2009).
  Article CAS PubMed Google Scholar
• Schiller, J., Schiller, Y., Stuart, G. & Sakmann, B. Calcium action potentials restricted to distal apical dendrites of rat neocortical pyramidal neurons. J. Physiol. 505, 605–616 (1997).
  Article CAS PubMed PubMed Central Google Scholar
• Golding, N. L., Staff, N. P. & Spruston, N. Dendritic spikes as a mechanism for cooperative long-term potentiation. Nature 418, 326–331 (2002).
  Article CAS PubMed Google Scholar
• Hardie, J. & Spruston, N. Synaptic depolarization is more effective than back-propagating action potentials during induction of associative long-term potentiation in hippocampal pyramidal neurons. J. Neurosci. 29, 3233–3241 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Losonczy, A., Makara, J. K. & Magee, J. C. Compartmentalized dendritic plasticity and input feature storage in neurons. Nature 452, 436–441 (2008).
  Article CAS PubMed Google Scholar
• Sjostrom, P. J., Rancz, E. A., Roth, A. & Hausser, M. Dendritic excitability and synaptic plasticity. Physiol. Rev. 88, 769–840 (2008).
  Article CAS PubMed Google Scholar
• Govindarajan, A., Israely, I., Huang, S. Y. & Tonegawa, S. The dendritic branch is the preferred integrative unit for protein synthesis-dependent LTP. Neuron 69, 132–146 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Kang, H. & Schuman, E. M. A requirement for local protein synthesis in neurotrophin-induced hippocampal synaptic plasticity. Science 273, 1402–1406 (1996).
  Article CAS PubMed Google Scholar
• Ariav, G., Polsky, A. & Schiller, J. Submillisecond precision of the input–output transformation function mediated by fast sodium dendritic spikes in basal dendrites of CA1 pyramidal neurons. J. Neurosci. 23, 7750–7758 (2003).
  Article CAS PubMed PubMed Central Google Scholar
• d’Aquin, S. et al. Compartmentalized dendritic plasticity during associative learning. Science 376, eabf7052 (2022). This study provides powerful experimental evidence for the development of non-linear dendritic plasticity with learning.
  Article PubMed Google Scholar
• Cichon, J. & Gan, W. B. Branch-specific dendritic Ca2+ spikes cause persistent synaptic plasticity. Nature 520, 180–185 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Sheffield, M. E. & Dombeck, D. A. Calcium transient prevalence across the dendritic arbour predicts place field properties. Nature 517, 200–204 (2015).
  Article CAS PubMed Google Scholar
• Voigts, J. & Harnett, M. T. Somatic and dendritic encoding of spatial variables in retrosplenial cortex differs during 2D navigation. Neuron 105, 237–245.e4 (2020).
  Article CAS PubMed Google Scholar
• Schoenfeld, G. et al. Dendritic integration of sensory and reward information facilitates learning. Preprint at bioRxiv https://doi.org/10.1101/2021.12.28.474360 (2021).
• Polsky, A., Mel, B. W. & Schiller, J. Computational subunits in thin dendrites of pyramidal cells. Nat. Neurosci. 7, 621–627 (2004).
  Article CAS PubMed Google Scholar
• Katz, Y. et al. Synapse distribution suggests a two-stage model of dendritic integration in CA1 pyramidal neurons. Neuron 63, 171–177 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Poirazi, P., Brannon, T. & Mel, B. W. Pyramidal neuron as two-layer neural network. Neuron 37, 989–999 (2003).
  Article CAS PubMed Google Scholar
• Tzilivaki, A., Kastellakis, G. & Poirazi, P. Challenging the point neuron dogma: FS basket cells as 2-stage nonlinear integrators. Nat. Commun. 10, 3664 (2019).
  Article PubMed PubMed Central Google Scholar
• Branco, T. & Hausser, M. The single dendritic branch as a fundamental functional unit in the nervous system. Curr. Opin. Neurobiol. 20, 494–502 (2010).
  Article CAS PubMed Google Scholar
• Traub, R. D. & Llinas, R. Hippocampal pyramidal cells: significance of dendritic ionic conductances for neuronal function and epileptogenesis. J. Neurophysiol. 42, 476–496 (1979).
  Article CAS PubMed Google Scholar
• Magee, J. C. Dendritic integration of excitatory synaptic input. Nat. Rev. Neurosci. 1, 181–190 (2000).
  Article CAS PubMed Google Scholar
• Kastellakis, G., Silva, A. J. & Poirazi, P. Linking memories across time via neuronal and dendritic overlaps in model neurons with active dendrites. Cell Rep. 17, 1491–1504 (2016). This modelling study provides powerful insights into memory linking, especially with regards to dendritic allocation.
  Article CAS PubMed PubMed Central Google Scholar
• Poirazi, P., Brannon, T. & Mel, B. W. Arithmetic of subthreshold synaptic summation in a model CA1 pyramidal cell. Neuron 37, 977–987 (2003).
  Article CAS PubMed Google Scholar
• Behabadi, B. F., Polsky, A., Jadi, M., Schiller, J. & Mel, B. W. Location-dependent excitatory synaptic interactions in pyramidal neuron dendrites. PLoS Comput. Biol. 8, e1002599 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Branco, T. & Hausser, M. Synaptic integration gradients in single cortical pyramidal cell dendrites. Neuron 69, 885–892 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Abraham, W. C. & Bear, M. F. Metaplasticity: the plasticity of synaptic plasticity. Trends Neurosci. 19, 126–130 (1996).
  Article CAS PubMed Google Scholar
• Mockett, B. G. & Hulme, S. R. Metaplasticity: new insights through electrophysiological investigations. J. Integr. Neurosci. 7, 315–336 (2008).
  Article PubMed Google Scholar
• Frey, U. & Morris, R. G. Synaptic tagging and long-term potentiation. Nature 385, 533–536 (1997).
  Article CAS PubMed Google Scholar
• Frey, U. & Morris, R. G. Synaptic tagging: implications for late maintenance of hippocampal long-term potentiation. Trends Neurosci. 21, 181–188 (1998).
  Article CAS PubMed Google Scholar
• Redondo, R. L. & Morris, R. G. Making memories last: the synaptic tagging and capture hypothesis. Nat. Rev. Neurosci. 12, 17–30 (2011).
  Article CAS PubMed Google Scholar
• Steward, O. & Schuman, E. M. Protein synthesis at synaptic sites on dendrites. Annu. Rev. Neurosci. 24, 299–325 (2001).
  Article CAS PubMed Google Scholar
• Sajikumar, S. & Frey, J. U. Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD. Neurobiol. Learn. Mem. 82, 12–25 (2004).
  Article CAS PubMed Google Scholar
• Toni, N., Buchs, P. A., Nikonenko, I., Bron, C. R. & Muller, D. LTP promotes formation of multiple spine synapses between a single axon terminal and a dendrite. Nature 402, 421–425 (1999).
  Article CAS PubMed Google Scholar
• Harvey, C. D., Yasuda, R., Zhong, H. & Svoboda, K. The spread of Ras activity triggered by activation of a single dendritic spine. Science 321, 136–140 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Patterson, M. A., Szatmari, E. M. & Yasuda, R. AMPA receptors are exocytosed in stimulated spines and adjacent dendrites in a Ras-ERK-dependent manner during long-term potentiation. Proc. Natl Acad. Sci. USA 107, 15951–15956 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Moncada, D. & Viola, H. Induction of long-term memory by exposure to novelty requires protein synthesis: evidence for a behavioral tagging. J. Neurosci. 27, 7476–7481 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Wang, S. H., Redondo, R. L. & Morris, R. G. Relevance of synaptic tagging and capture to the persistence of long-term potentiation and everyday spatial memory. Proc. Natl Acad. Sci. USA 107, 19537–19542 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Izquierdo, I., Schroder, N., Netto, C. A. & Medina, J. H. Novelty causes time-dependent retrograde amnesia for one-trial avoidance in rats through NMDA receptor- and CaMKII-dependent mechanisms in the hippocampus. Eur. J. Neurosci. 11, 3323–3328 (1999).
  Article CAS PubMed Google Scholar
• Kastellakis, G., Cai, D. J., Mednick, S. C., Silva, A. J. & Poirazi, P. Synaptic clustering within dendrites: an emerging theory of memory formation. Prog. Neurobiol. 126, 19–35 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Mel, B. W. Synaptic integration in an excitable dendritic tree. J. Neurophysiol. 70, 1086–1101 (1993).
  Article CAS PubMed Google Scholar
• McBride, T. J., Rodriguez-Contreras, A., Trinh, A., Bailey, R. & Debello, W. M. Learning drives differential clustering of axodendritic contacts in the barn owl auditory system. J. Neurosci. 28, 6960–6973 (2008).
  Article CAS PubMed PubMed Central Google Scholar
• Takahashi, N. et al. Locally synchronized synaptic inputs. Science 335, 353–356 (2012).
  Article CAS PubMed Google Scholar
• Iacaruso, M. F., Gasler, I. T. & Hofer, S. B. Synaptic organization of visual space in primary visual cortex. Nature 547, 449–452 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Caze, R. D., Jarvis, S., Foust, A. J. & Schultz, S. R. Dendrites enable a robust mechanism for neuronal stimulus selectivity. Neural Comput. 29, 2511–2527 (2017).
  Article PubMed Google Scholar
• Chen, X., Leischner, U., Rochefort, N. L., Nelken, I. & Konnerth, A. Functional mapping of single spines in cortical neurons in vivo. Nature 475, 501–505 (2011).
  Article CAS PubMed Google Scholar
• Jia, H., Rochefort, N. L., Chen, X. & Konnerth, A. Dendritic organization of sensory input to cortical neurons in vivo. Nature 464, 1307–1312 (2010).
  Article CAS PubMed Google Scholar
• Varga, Z., Jia, H., Sakmann, B. & Konnerth, A. Dendritic coding of multiple sensory inputs in single cortical neurons in vivo. Proc. Natl Acad. Sci. USA 108, 15420–15425 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Frank, A. C. et al. Hotspots of dendritic spine turnover facilitate clustered spine addition and learning and memory. Nat. Commun. 9, 422 (2018).
  Article PubMed PubMed Central Google Scholar
• Fu, M., Yu, X., Lu, J. & Zuo, Y. Repetitive motor learning induces coordinated formation of clustered dendritic spines in vivo. Nature 483, 92–95 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Lee, K. S., Vandemark, K., Mezey, D., Shultz, N. & Fitzpatrick, D. Functional synaptic architecture of callosal inputs in mouse primary visual cortex. Neuron 101, 421–428.e5 (2019).
  Article CAS PubMed PubMed Central Google Scholar
• Druckmann, S. et al. Structured synaptic connectivity between hippocampal regions. Neuron 81, 629–640 (2014).
  Article CAS PubMed Google Scholar
• Harvey, C. D. & Svoboda, K. Locally dynamic synaptic learning rules in pyramidal neuron dendrites. Nature 450, 1195–1200 (2007).
  Article CAS PubMed PubMed Central Google Scholar
• Pancholi, R., Ryan, L. & Peron, S. Learning in a sensory cortical microstimulation task is associated with elevated representational stability. Nat. Commun. 14, 3860 (2023).
  Article CAS PubMed PubMed Central Google Scholar
• Sharif, F., Tayebi, B., Buzsaki, G., Royer, S. & Fernandez-Ruiz, A. Subcircuits of deep and superficial CA1 place cells support efficient spatial coding across heterogeneous environments. Neuron 109, 363–376.e6 (2021).
  Article CAS PubMed Google Scholar
• Wienbar, S. & Schwartz, G. W. Differences in spike generation instead of synaptic inputs determine the feature selectivity of two retinal cell types. Neuron 110, 2110–2123.e4 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Yuan, Q., Isaacson, J. S. & Scanziani, M. Linking neuronal ensembles by associative synaptic plasticity. PLoS ONE 6, e20486 (2011). This study displays the fluidity of hippocampal ensembles.
  Article CAS PubMed PubMed Central Google Scholar
• Abdou, K. et al. Inspiring cognitive inference in a cortical network during REM sleep. Preprint at bioRxiv https://doi.org/10.1101/2021.04.08.439095 (2021).
• Losonczy, A. & Magee, J. C. Integrative properties of radial oblique dendrites in hippocampal CA1 pyramidal neurons. Neuron 50, 291–307 (2006).
  Article CAS PubMed Google Scholar
• Niculescu, D. et al. A BDNF-mediated push–pull plasticity mechanism for synaptic clustering. Cell Rep. 24, 2063–2074 (2018).
  Article CAS PubMed Google Scholar
• Fauth, M. J. & van Rossum, M. C. Self-organized reactivation maintains and reinforces memories despite synaptic turnover. eLife 8, e43717 (2019).
  Article PubMed PubMed Central Google Scholar
• van de Ven, G. M., Trouche, S., McNamara, C. G., Allen, K. & Dupret, D. Hippocampal offline reactivation consolidates recently formed cell assembly patterns during sharp wave-ripples. Neuron 92, 968–974 (2016).
  Article PubMed PubMed Central Google Scholar
• Joensen, B. H. et al. Targeted memory reactivation during sleep can induce forgetting of overlapping memories. Learn. Mem. 29, 401–411 (2022).
  Article PubMed PubMed Central Google Scholar
• Chanales, A. J. H., Oza, A., Favila, S. E. & Kuhl, B. A. Overlap among spatial memories triggers repulsion of hippocampal representations. Curr. Biol. 27, 2307–2317.e5 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Kerren, C., van Bree, S., Griffiths, B. J. & Wimber, M. Phase separation of competing memories along the human hippocampal theta rhythm. eLife 11, e80633 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Das, T., Ivleva, E. I., Wagner, A. D., Stark, C. E. & Tamminga, C. A. Loss of pattern separation performance in schizophrenia suggests dentate gyrus dysfunction. Schizophr. Res. 159, 193–197 (2014).
  Article PubMed PubMed Central Google Scholar
• Manschreck, T. C. et al. Semantic priming in thought disordered schizophrenic patients. Schizophr. Res. 1, 61–66 (1988).
  Article CAS PubMed Google Scholar
• Treffert, D. A. The savant syndrome: an extraordinary condition. A synopsis: past, present, future. Philos. Trans. R. Soc. Lond. B Biol. Sci. 364, 1351–1357 (2009).
  Article PubMed PubMed Central Google Scholar
• Cohn-Sheehy, B. I. et al. Narratives bridge the divide between distant events in episodic memory. Mem. Cogn. 50, 478–494 (2022).
  Article Google Scholar
• Murphy, G., Loftus, E., Levine, L. J., Grady, R. H. & Greene, C. M. Weak correlations among 13 episodic memory tasks related to the same public event. Appl. Cogn. Psychol. 37, 1045–1058 (2023).
  Article Google Scholar
• Zou, F. et al. Re-expression of CA1 and entorhinal activity patterns preserves temporal context memory at long timescales. Nat. Commun. 14, 4350 (2023).
  Article CAS PubMed PubMed Central Google Scholar
• Terada, S. et al. Adaptive stimulus selection for consolidation in the hippocampus. Nature 601, 240–244 (2022). This work demonstrates the selective nature of neuronal reactivation during rest.
  Article CAS PubMed Google Scholar
• Carr, M. F., Jadhav, S. P. & Frank, L. M. Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nat. Neurosci. 14, 147–153 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Joo, H. R. & Frank, L. M. The hippocampal sharp wave-ripple in memory retrieval for immediate use and consolidation. Nat. Rev. Neurosci. 19, 744–757 (2018).
  Article CAS PubMed PubMed Central Google Scholar
• Swanson, R. A., Levenstein, D., McClain, K., Tingley, D. & Buzsaki, G. Variable specificity of memory trace reactivation during hippocampal sharp wave ripples. Curr. Opin. Behav. Sci. 32, 126–135 (2020).
  Article PubMed PubMed Central Google Scholar
• Hahamy, A., Dubossarsky, H. & Behrens, T. E. J. The human brain reactivates context-specific past information at event boundaries of naturalistic experiences. Nat. Neurosci. 26, 1080–1089 (2023).
  Article CAS PubMed PubMed Central Google Scholar
• Zaki, Y. et al. Aversive experience drives offline ensemble reactivation to link memories across days. Preprint at bioRxiv https://doi.org/10.1101/2023.03.13.532469 (2023).
• Pereira, S. I. R. & Lewis, P. A. The differing roles of NREM and REM sleep in the slow enhancement of skills and schemas. Curr. Opin. Physiol. 15, 82–88 (2020).
  Article Google Scholar
• Giuditta, A. Sleep memory processing: the sequential hypothesis. Front. Syst. Neurosci. 8, 219 (2014).
  Article PubMed PubMed Central Google Scholar
• Cairney, S. A., Ashton, J. E., Roshchupkina, A. A. & Sobczak, J. M. A dual role for sleep spindles in sleep-dependent memory consolidation? J. Neurosci. 35, 12328–12330 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Sara, S. J. Sleep to remember. J. Neurosci. 37, 457–463 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Poe, G. R. Sleep is for forgetting. J. Neurosci. 37, 464–473 (2017).
  Article CAS PubMed PubMed Central Google Scholar
• Kaida, K., Mori, I., Kihara, K. & Kaida, N. The function of REM and NREM sleep on memory distortion and consolidation. Neurobiol. Learn. Mem. 204, 107811 (2023).
  Article PubMed Google Scholar
• Mildner, J. N. & Tamir, D. I. Spontaneous thought as an unconstrained memory process. Trends Neurosci. 42, 763–777 (2019).
  Article CAS PubMed Google Scholar
• Liu, Y., Dolan, R. J., Kurth-Nelson, Z. & Behrens, T. E. J. Human replay spontaneously reorganizes experience. Cell 178, 640–652.e614 (2019). This study showcases retrospective recollection and reorganization of experiences.
  Article CAS PubMed PubMed Central Google Scholar
• Wang, Y., Deng, Y., Cao, L., Zhang, J. & Yang, L. Retrospective memory integration accompanies reconfiguration of neural cell assemblies. Hippocampus 32, 179–192 (2022). This network model displays many features of retrospective memory processing, and the reconfiguration of neuronal coding as associations are formed.
  Article PubMed Google Scholar
• Ferbinteanu, J. & Shapiro, M. L. Prospective and retrospective memory coding in the hippocampus. Neuron 40, 1227–1239 (2003).
  Article CAS PubMed Google Scholar
• Pereira, U. & Brunel, N. Attractor dynamics in networks with learning rules inferred from in vivo data. Neuron 99, 227–238.e4 (2018).
  Article CAS PubMed PubMed Central Google Scholar
• Naim, M., Katkov, M., Romani, S. & Tsodyks, M. Fundamental law of memory recall. Phys. Rev. Lett. 124, 018101 (2020).
  Article CAS PubMed Google Scholar
• Ghandour, K. & Inokuchi, K. Memory reactivations during sleep. Neurosci. Res. 189, 60–65 (2023).
  Article CAS PubMed Google Scholar
• King, B. R., Gann, M. A., Mantini, D., Doyon, J. & Albouy, G. Persistence of hippocampal and striatal multivoxel patterns during awake rest after motor sequence learning. iScience 25, 105498 (2022).
  Article CAS PubMed PubMed Central Google Scholar
• Staresina, B. P., Alink, A., Kriegeskorte, N. & Henson, R. N. Awake reactivation predicts memory in humans. Proc. Natl Acad. Sci. USA 110, 21159–21164 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Tambini, A. & Davachi, L. Persistence of hippocampal multivoxel patterns into postencoding rest is related to memory. Proc. Natl Acad. Sci. USA 110, 19591–19596 (2013).
  Article CAS PubMed PubMed Central Google Scholar
• Tambini, A., Ketz, N. & Davachi, L. Enhanced brain correlations during rest are related to memory for recent experiences. Neuron 65, 280–290 (2010).
  Article CAS PubMed PubMed Central Google Scholar
• Zhang, H., Fell, J. & Axmacher, N. Electrophysiological mechanisms of human memory consolidation. Nat. Commun. 9, 4103 (2018).
  Article PubMed PubMed Central Google Scholar
• Nader, K., Schafe, G. E. & Le Doux, J. E. Fear memories require protein synthesis in the amygdala for reconsolidation after retrieval. Nature 406, 722–726 (2000).
  Article CAS PubMed Google Scholar
• Walker, M. P., Brakefield, T., Hobson, J. A. & Stickgold, R. Dissociable stages of human memory consolidation and reconsolidation. Nature 425, 616–620 (2003).
  Article CAS PubMed Google Scholar
• Collin, S. H., Milivojevic, B. & Doeller, C. F. Memory hierarchies map onto the hippocampal long axis in humans. Nat. Neurosci. 18, 1562–1564 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Strange, B. A., Witter, M. P., Lein, E. S. & Moser, E. I. Functional organization of the hippocampal longitudinal axis. Nat. Rev. Neurosci. 15, 655–669 (2014).
  Article CAS PubMed Google Scholar
• MacDonald, C. J., Lepage, K. Q., Eden, U. T. & Eichenbaum, H. Hippocampal “time cells” bridge the gap in memory for discontiguous events. Neuron 71, 737–749 (2011).
  Article CAS PubMed PubMed Central Google Scholar
• Umbach, G. et al. Time cells in the human hippocampus and entorhinal cortex support episodic memory. Proc. Natl Acad. Sci. USA 117, 28463–28474 (2020).
  Article CAS PubMed PubMed Central Google Scholar
• Guderian, S., Schott, B. H., Richardson-Klavehn, A. & Duzel, E. Medial temporal theta state before an event predicts episodic encoding success in humans. Proc. Natl Acad. Sci. USA 106, 5365–5370 (2009).
  Article CAS PubMed PubMed Central Google Scholar
• Park, H. & Rugg, M. D. Prestimulus hippocampal activity predicts later recollection. Hippocampus 20, 24–28 (2010).
  Article PubMed PubMed Central Google Scholar
• van Dongen, E. V., Takashima, A., Barth, M. & Fernandez, G. Functional connectivity during light sleep is correlated with memory performance for face–location associations. Neuroimage 57, 262–270 (2011).
  Article PubMed Google Scholar
• Yoo, J. J. et al. When the brain is prepared to learn: enhancing human learning using real-time fMRI. Neuroimage 59, 846–852 (2012).
  Article PubMed Google Scholar
• Urgolites, Z. J. et al. Spiking activity in the human hippocampus prior to encoding predicts subsequent memory. Proc. Natl Acad. Sci. USA 117, 13767–13770 (2020).
  Article CAS PubMed PubMed Central Google Scholar
• Schapiro, A. C., Kustner, L. V. & Turk-Browne, N. B. Shaping of object representations in the human medial temporal lobe based on temporal regularities. Curr. Biol. 22, 1622–1627 (2012).
  Article CAS PubMed PubMed Central Google Scholar
• Ezzyat, Y. & Davachi, L. Similarity breeds proximity: pattern similarity within and across contexts is related to later mnemonic judgments of temporal proximity. Neuron 81, 1179–1189 (2014).
  Article CAS PubMed PubMed Central Google Scholar
• Yetton, B. D., Cai, D. J., Spoormaker, V. I., Silva, A. J. & Mednick, S. C. Human memories can be linked by temporal proximity. Front. Hum. Neurosci. 13, 315 (2019).
  Article PubMed PubMed Central Google Scholar
• Hupbach, A., Gomez, R., Hardt, O. & Nadel, L. Reconsolidation of episodic memories: a subtle reminder triggers integration of new information. Learn. Mem. 14, 47–53 (2007).
  Article PubMed PubMed Central Google Scholar
• Jones, B., Bukoski, E., Nadel, L. & Fellous, J. M. Remaking memories: reconsolidation updates positively motivated spatial memory in rats. Learn. Mem. 19, 91–98 (2012).
  Article PubMed PubMed Central Google Scholar
• Elliott, R., Rubinsztein, J. S., Sahakian, B. J. & Dolan, R. J. The neural basis of mood-congruent processing biases in depression. Arch. Gen. Psychiatry 59, 597–604 (2002).
  Article PubMed Google Scholar
• Lewis, P. A., Critchley, H. D., Smith, A. P. & Dolan, R. J. Brain mechanisms for mood congruent memory facilitation. Neuroimage 25, 1214–1223 (2005).
  Article CAS PubMed Google Scholar
• Ramirez, S. et al. Activating positive memory engrams suppresses depression-like behaviour. Nature 522, 335–339 (2015).
  Article CAS PubMed PubMed Central Google Scholar
• Bierbrauer, A., Fellner, M. C., Heinen, R., Wolf, O. T. & Axmacher, N. The memory trace of a stressful episode. Curr. Biol. 31, 5204–5213.e8 (2021).
  Article CAS PubMed Google Scholar