Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The neurobiological foundation of memory retrieval

Nature Neuroscience volume 22, pages 1576–1585 (2019)Cite this article

Subjects

Abstract

Memory retrieval involves the interaction between external sensory or internally generated cues and stored memory traces (or engrams) in a process termed ‘ecphory’. While ecphory has been examined in human cognitive neuroscience research, its neurobiological foundation is less understood. To the extent that ecphory involves ‘reawakening’ of engrams, leveraging recently developed technologies that can identify and manipulate engrams in rodents provides a fertile avenue for examining retrieval at the level of neuronal ensembles. Here we evaluate emerging neuroscientific research of this type, using cognitive theory as a guiding principle to organize and interpret initial findings. Our Review highlights the critical interaction between engrams and retrieval cues (environmental or artificial) for memory accessibility and retrieval success. These findings also highlight the intimate relationship between the mechanisms important in forming engrams and those important in their recovery, as captured in the cognitive notion of ‘encoding specificity’. Finally, we identify several questions that currently remain unanswered.

From this work, Tulving developed an important conceptual distinction between availability versus accessibility of information in memory. According to this view2,3, some forms of memory failure reflect a lack of availability of pertinent information (i.e., permanent loss), whereas other forms of memory failure reflect temporary problems in accessibility. Phenomenologically, this relates to the common ‘tip of the tongue’ experience, in which one might struggle to recall a familiar name or place while having the strong impression that the information is present. Indeed, often this information subsequently comes to mind. Cues available at retrieval represent perhaps the most critical factor that determines memory accessibility and corresponding success at remembering.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Tulving and Pearlstone’s experiment on retrieval failure1.
Fig. 2: Preventing and inducing ecphory by direct manipulation of fear memory engrams.
Fig. 3: Ecphory for an artificially generated engram.
Fig. 4: Silencing of the engram. Engrams exist in different states of accessibility.

References

  1. Tulving, E. & Pearlstone, Z. Availability versus accessibility of information in memory for words. J. Verbal Learn. Verbal Behav. 5, 381–391 (1966).

    Article  Google Scholar 

  2. Tulving, E. Ecphoric processes in episodic memory. Philos. Trans. R. Soc. Lond. B 302, 361–370 (1983).

    Article  Google Scholar 

  3. Tulving, E. Elements of Episodic Memory. (Oxford University Press, 1983).

  4. Semon, R. Die Mneme. (W. Engelmann, 1904).

  5. Josselyn, S. A., Köhler, S. & Frankland, P. W. Heroes of the engram. J. Neurosci. 37, 4647–4657 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tulving, E. Episodic memory: from mind to brain. Annu. Rev. Psychol. 53, 1–25 (2002).

    Article  PubMed  Google Scholar 

  7. Eichenbaum, H. Still searching for the engram. Learn. Behav. 44, 209–222 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Josselyn, S. A., Köhler, S. & Frankland, P. W. Finding the engram. Nat. Rev. Neurosci. 16, 521–534 (2015).

    Article  CAS  PubMed  Google Scholar 

  9. 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 

  10. Tonegawa, S., Pignatelli, M., Roy, D. S. & Ryan, T. J. Memory engram storage and retrieval. Curr. Opin. Neurobiol. 35, 101–109 (2015).

    Article  CAS  PubMed  Google Scholar 

  11. DeNardo, L. A. et al. Temporal evolution of cortical ensembles promoting remote memory retrieval. Nat. Neurosci. 22, 460–469 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Denny, C. A. et al. Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron 83, 189–201 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 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 

  14. Sørensen, A. T. et al. A robust activity marking system for exploring active neuronal ensembles. eLife 5, e13918 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Josselyn, S. A. & Frankland, P. W. Memory allocation: mechanisms and function. Annu. Rev. Neurosci. 41, 389–413 (2018).

    Article  CAS  PubMed  Google Scholar 

  16. Ben-Yakov, A., Dudai, Y. & Mayford, M. R. Memory retrieval in mice and men. Cold Spring Harb. Perspect. Biol. 7, a021790 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Robins, S. K. Memory and optogenetic intervention: separating the engram from the ecphory. Philos. Sci. 85, 1078–1089 (2018).

    Article  Google Scholar 

  18. Denny, C. A., Lebois, E. & Ramirez, S. From engrams to pathologies of the brain. Front. Neural Circuits 11, 23 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. 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 

  20. Han, J. H. et al. Selective erasure of a fear memory. Science 323, 1492–1496 (2009).

    Article  CAS  PubMed  Google Scholar 

  21. 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 

  22. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. 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 

  24. Hsiang, H. L. et al. Manipulating a “cocaine engram” in mice. J. Neurosci. 34, 14115–14127 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Lacagnina, A. F. et al. Distinct hippocampal engrams control extinction and relapse of fear memory. Nat. Neurosci. 22, 753–761 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Liu, X. et al. Optogenetic stimulation of a hippocampal engram activates fear memory recall. Nature 484, 381–385 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 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 

  28. Kim, J., Kwon, J. T., Kim, H. S., Josselyn, S. A. & Han, J. H. Memory recall and modifications by activating neurons with elevated CREB. Nat. Neurosci. 17, 65–72 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Abdou, K. et al. Synapse-specific representation of the identity of overlapping memory engrams. Science 360, 1227–1231 (2018).

    Article  CAS  PubMed  Google Scholar 

  30. Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A. & Tonegawa, S. Memory. Engram cells retain memory under retrograde amnesia. Science 348, 1007–1013 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Redondo, R. L. et al. Bidirectional switch of the valence associated with a hippocampal contextual memory engram. Nature 513, 426–430 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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 

  33. Vetere, G. et al. Memory formation in the absence of experience. Nat. Neurosci. 22, 933–940 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Roy, D. S., Muralidhar, S., Smith, L. M. & Tonegawa, S. Silent memory engrams as the basis for retrograde amnesia. Proc. Natl. Acad. Sci. USA 114, E9972–E9979 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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 

  36. Suzuki, A. et al. Memory reconsolidation and extinction have distinct temporal and biochemical signatures. J. Neurosci. 24, 4787–4795 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Roy, D. S. et al. Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease. Nature 531, 508–512 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Perusini, J. N. et al. Optogenetic stimulation of dentate gyrus engrams restores memory in Alzheimer’s disease mice. Hippocampus 27, 1110–1122 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Guskjolen, A. et al. Recovery of “lost” infant memories in mice. Curr. Biol. 28, 2283–2290.e3 (2018).

    Article  CAS  PubMed  Google Scholar 

  40. Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S. & Tonegawa, S. Ventral CA1 neurons store social memory. Science 353, 1536–1541 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Choi, J. H. et al. Interregional synaptic maps among engram cells underlie memory formation. Science 360, 430–435 (2018).

    Article  CAS  PubMed  Google Scholar 

  42. Gouty-Colomer, L. A. et al. Arc expression identifies the lateral amygdala fear memory trace. Mol. Psychiatry 21, 364–375 (2016).

    Article  CAS  PubMed  Google Scholar 

  43. Nabavi, S. et al. Engineering a memory with LTD and LTP. Nature 511, 348–352 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schacter, D.L. Searching for Memory: The Brain, the Mind, and the Past. (Basic Books, 1996).

  45. Roy, D. S., Okuyama, T. & Tonegawa, S. Tagging activated neurons with light. Nat. Biotechnol. 35, 827–828 (2017).

    Article  CAS  PubMed  Google Scholar 

  46. Davis, R. L. & Zhong, Y. The biology of forgetting—a perspective. Neuron 95, 490–503 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Frankland, P. W., Köhler, S. & Josselyn, S. A. Hippocampal neurogenesis and forgetting. Trends Neurosci. 36, 497–503 (2013).

    Article  CAS  PubMed  Google Scholar 

  48. Hardt, O., Nader, K. & Nadel, L. Decay happens: the role of active forgetting in memory. Trends Cogn. Sci. 17, 111–120 (2013).

    Article  PubMed  Google Scholar 

  49. Tulving, E. & Thomson, D. M. Encoding specificity and retrieval processes in episodic memory. Psychol. Rev. 80, 352–373 (1973).

    Article  Google Scholar 

  50. Eich, E. Mood as a mediator of place dependent memory. J. Exp. Psychol. Gen. 124, 293–308 (1995).

    Article  CAS  PubMed  Google Scholar 

  51. Godden, D. R. & Baddeley, A. D. Context‐dependent memory in two natural environments: On land and underwater. Br. J. Psychol. 66, 325–331 (1975).

    Article  Google Scholar 

  52. Smith, S. M. & Vela, E. Environmental context-dependent memory: a review and meta-analysis. Psychon. Bull. Rev. 8, 203–220 (2001).

    Article  CAS  PubMed  Google Scholar 

  53. Bouton, M. E. Context, time, and memory retrieval in the interference paradigms of Pavlovian learning. Psychol. Bull. 114, 80–99 (1993).

    Article  CAS  PubMed  Google Scholar 

  54. Maren, S., Phan, K. L. & Liberzon, I. The contextual brain: implications for fear conditioning, extinction and psychopathology. Nat. Rev. Neurosci. 14, 417–428 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Jafarpour, A., Fuentemilla, L., Horner, A. J., Penny, W. & Duzel, E. Replay of very early encoding representations during recollection. J. Neurosci. 34, 242–248 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Johnson, J. D., McDuff, S. G., Rugg, M. D. & Norman, K. A. Recollection, familiarity, and cortical reinstatement: a multivoxel pattern analysis. Neuron 63, 697–708 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Manning, J. R., Polyn, S. M., Baltuch, G. H., Litt, B. & Kahana, M. J. Oscillatory patterns in temporal lobe reveal context reinstatement during memory search. Proc. Natl. Acad. Sci. USA 108, 12893–12897 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Polyn, S. M., Natu, V. S., Cohen, J. D. & Norman, K. A. Category-specific cortical activity precedes retrieval during memory search. Science 310, 1963–1966 (2005).

    Article  CAS  PubMed  Google Scholar 

  59. Ritchey, M., Wing, E. A., LaBar, K. S. & Cabeza, R. Neural similarity between encoding and retrieval is related to memory via hippocampal interactions. Cereb. Cortex 23, 2818–2828 (2013).

    Article  PubMed  Google Scholar 

  60. Staresina, B. P., Henson, R. N., Kriegeskorte, N. & Alink, A. Episodic reinstatement in the medial temporal lobe. J. Neurosci. 32, 18150–18156 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Staresina, B. P. et al. Hippocampal pattern completion is linked to gamma power increases and alpha power decreases during recollection. eLife 5, e17397 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Yaffe, R. B. et al. Reinstatement of distributed cortical oscillations occurs with precise spatiotemporal dynamics during successful memory retrieval. Proc. Natl. Acad. Sci. USA 111, 18727–18732 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. St-Laurent, M., Abdi, H. & Buchsbaum, B. R. Distributed patterns of reactivation predict vividness of recollection. J. Cogn. Neurosci. 27, 2000–2018 (2015).

    Article  PubMed  Google Scholar 

  64. Danker, J. F., Tompary, A. & Davachi, L. Trial-by-trial hippocampal encoding activation predicts the fidelity of cortical reinstatement during subsequent retrieval. Cereb. Cortex 27, 3515–3524 (2017).

    PubMed  Google Scholar 

  65. Horner, A. J., Bisby, J. A., Bush, D., Lin, W. J. & Burgess, N. Evidence for holistic episodic recollection via hippocampal pattern completion. Nat. Commun. 6, 7462 (2015).

    Article  PubMed  Google Scholar 

  66. Staresina, B. P., Cooper, E. & Henson, R. N. Reversible information flow across the medial temporal lobe: the hippocampus links cortical modules during memory retrieval. J. Neurosci. 33, 14184–14192 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Staudigl, T., Vollmar, C., Noachtar, S. & Hanslmayr, S. Temporal-pattern similarity analysis reveals the beneficial and detrimental effects of context reinstatement on human memory. J. Neurosci. 35, 5373–5384 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. 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 

  69. Deng, W., Mayford, M. & Gage, F. H. Selection of distinct populations of dentate granule cells in response to inputs as a mechanism for pattern separation in mice. eLife 2, e00312 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  70. Khalaf, O. et al. Reactivation of recall-induced neurons contributes to remote fear memory attenuation. Science 360, 1239–1242 (2018).

    Article  CAS  PubMed  Google Scholar 

  71. Ramirez, S. et al. Creating a false memory in the hippocampus. Science 341, 387–391 (2013).

    Article  CAS  PubMed  Google Scholar 

  72. Tayler, K. K., Tanaka, K. Z., Reijmers, L. G. & Wiltgen, B. J. Reactivation of neural ensembles during the retrieval of recent and remote memory. Curr. Biol. 23, 99–106 (2013).

    Article  CAS  PubMed  Google Scholar 

  73. Richards, B. A. & Frankland, P. W. The conjunctive trace. Hippocampus 23, 207–212 (2013).

    Article  PubMed  Google Scholar 

  74. Orsini, C. A., Yan, C. & Maren, S. Ensemble coding of context-dependent fear memory in the amygdala. Front. Behav. Neurosci. 7, 199 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  75. Emiliani, V., Cohen, A. E., Deisseroth, K. & Häusser, M. All-optical interrogation of neural circuits. J. Neurosci. 35, 13917–13926 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Yang, S. J. et al. Extended field-of-view and increased-signal 3D holographic illumination with time-division multiplexing. Opt. Express 23, 32573–32581 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Yang, W. & Yuste, R. Holographic imaging and photostimulation of neural activity. Curr. Opin. Neurobiol. 50, 211–221 (2018).

    Article  CAS  PubMed  Google Scholar 

  78. Carrillo-Reid, L., Han, S., Yang, W., Akrouh, A. & Yuste, R. Controlling visually guided behavior by holographic recalling of cortical ensembles. Cell 178, 447–457.e5 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Marshel, J. H. et al. Cortical layer-specific critical dynamics triggering perception. Science 365, eaaw5202 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Squire, L. R. & Alvarez, P. Retrograde amnesia and memory consolidation: a neurobiological perspective. Curr. Opin. Neurobiol. 5, 169–177 (1995).

    Article  CAS  PubMed  Google Scholar 

  81. Teyler, T. J. & DiScenna, P. The hippocampal memory indexing theory. Behav. Neurosci. 100, 147–154 (1986).

    Article  CAS  PubMed  Google Scholar 

  82. 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, 419–457 (1995).

    Article  PubMed  Google Scholar 

  83. Norman, K. A. & O’Reilly, R. C. Modeling hippocampal and neocortical contributions to recognition memory: a complementary-learning-systems approach. Psychol. Rev. 110, 611–646 (2003).

    Article  PubMed  Google Scholar 

  84. Josselyn, S. A. & Frankland, P. W. Infantile amnesia: a neurogenic hypothesis. Learn. Mem. 19, 423–433 (2012).

    Article  CAS  PubMed  Google Scholar 

  85. Wheeler, A. L. et al. Identification of a functional connectome for long-term fear memory in mice. PLOS Comput. Biol. 9, e1002853 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Vetere, G. et al. Chemogenetic interrogation of a brain-wide fear memory network in mice. Neuron 94, 363–374.e4 (2017).

    Article  CAS  PubMed  Google Scholar 

  87. 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).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Frankland, P. W. & Bontempi, B. The organization of recent and remote memories. Nat. Rev. Neurosci. 6, 119–130 (2005).

    Article  CAS  PubMed  Google Scholar 

  89. Rescorla, R.A. Pavlovian Second-order Conditioning (Psychology Revivals): Studies in Associative Learning. (Psychology Press, 2014).

  90. Ohkawa, N. et al. Artificial association of pre-stored information to generate a qualitatively new memory. Cell Rep. 11, 261–269 (2015).

    Article  CAS  PubMed  Google Scholar 

  91. Chen, B. K. et al. Artificially enhancing and suppressing hippocampus-mediated memories. Curr. Biol. 29, 1885–1894.e4 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Anderson, M. C. Rethinking interference theory: Executive control and the mechanisms of forgetting. J. Mem. Lang. 49, 415–445 (2003).

    Article  Google Scholar 

  93. Garner, A. R. et al. Generation of a synthetic memory trace. Science 335, 1513–1516 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Sekeres, M. J. et al. Recovering and preventing loss of detailed memory: differential rates of forgetting for detail types in episodic memory. Learn. Mem. 23, 72–82 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  95. Richards, B. A. & Frankland, P. W. The persistence and transience of memory. Neuron 94, 1071–1084 (2017).

    Article  CAS  PubMed  Google Scholar 

  96. Nadel, L. & Moscovitch, M. Memory consolidation, retrograde amnesia and the hippocampal complex. Curr. Opin. Neurobiol. 7, 217–227 (1997).

    Article  CAS  PubMed  Google Scholar 

  97. Kitamura, T. et al. Engrams and circuits crucial for systems consolidation of a memory. Science 356, 73–78 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. 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).

    Article  CAS  PubMed  Google Scholar 

  99. Schapiro, A. C., Turk-Browne, N. B., Botvinick, M. M. & Norman, K. A. Complementary learning systems within the hippocampus: a neural network modelling approach to reconciling episodic memory with statistical learning. Philos. Trans. R. Soc. Lond. B 372, 20160049 (2017).

    Article  Google Scholar 

  100. Cai, D. J. et al. A shared neural ensemble links distinct contextual memories encoded close in time. Nature 534, 115–118 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Yokose, J. et al. Overlapping memory trace indispensable for linking, but not recalling, individual memories. Science 355, 398–403 (2017).

    Article  CAS  PubMed  Google Scholar 

  102. Gilboa, A. & Marlatte, H. Neurobiology of schemas and schema-mediated memory. Trends Cogn. Sci. 21, 618–631 (2017).

    Article  PubMed  Google Scholar 

  103. Richards, B. A. et al. Patterns across multiple memories are identified over time. Nat. Neurosci. 17, 981–986 (2014).

    Article  CAS  PubMed  Google Scholar 

  104. Tse, D. et al. Schema-dependent gene activation and memory encoding in neocortex. Science 333, 891–895 (2011).

    Article  CAS  PubMed  Google Scholar 

  105. Barry, D. N. & Maguire, E. A. Remote memory and the hippocampus: a constructive critique. Trends Cogn. Sci. 23, 128–142 (2019).

    Article  PubMed  Google Scholar 

  106. Barry, D. N. & Maguire, E. A. Consolidating the case for transient hippocampal memory traces. Trends Cogn. Sci. 23, 635–636 (2019).

    Article  PubMed  Google Scholar 

  107. Moscovitch, M. & Nadel, L. Sculpting remote memory: enduring hippocampal traces and vmPFC reconstructive processes. Trends Cogn. Sci. 23, 634–635 (2019).

    Article  PubMed  Google Scholar 

  108. Han, J. H. et al. Neuronal competition and selection during memory formation. Science 316, 457–460 (2007).

    Article  CAS  PubMed  Google Scholar 

  109. Rogerson, T. et al. Molecular and cellular mechanisms for trapping and activating emotional memories. PLoS One 11, e0161655 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  110. Kawashima, T. et al. Functional labeling of neurons and their projections using the synthetic activity-dependent promoter E-SARE. Nat. Methods 10, 889–895 (2013).

    Article  CAS  PubMed  Google Scholar 

  111. 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).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank A.Ramsaran and A.Park for drawing the figures, and we thank T. Ryan for comments on an earlier draft of this manuscript. This work was supported by Canadian Institutes of Health Research grants to P.W.F. (FDN-143227) and S.A.J. (FDN-388455) and a Natural Sciences and Engineering Research Council Discovery grant to S.K. (RGPIN-5770).

Author information

Authors and Affiliations

  1. Program in Neurosciences & Mental Health, Hospital for Sick Children, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  2. Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  3. Department of Psychology, University of Toronto, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  4. Department of Physiology, University of Toronto, Toronto, Ontario, Canada

    Paul W. Frankland & Sheena A. Josselyn

  5. Child & Brain Development Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada

    Paul W. Frankland

  6. Brain, Mind & Consciousness Program, Canadian Institute for Advanced Research, Toronto, Ontario, Canada

    Sheena A. Josselyn

  7. Department of Psychology, University of Western Ontario, London, Ontario, Canada

    Stefan Köhler

  8. The Brain and Mind Institute, University of Western Ontario, London, Ontario, Canada

    Stefan Köhler

Authors
  1. Paul W. Frankland
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sheena A. Josselyn
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Köhler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Paul W. Frankland or Stefan Köhler.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information Nature Neuroscience thanks Stephen Maren and Steve Ramirez for their contribution to the peer review of this work.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Frankland, P.W., Josselyn, S.A. & Köhler, S. The neurobiological foundation of memory retrieval. Nat Neurosci 22, 1576–1585 (2019). https://doi.org/10.1038/s41593-019-0493-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41593-019-0493-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing