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A single standard for memory: the case for reconsolidation

Nature Reviews Neuroscience volume 10, pages 224–234 (2009)Cite this article

Key Points

  • The terms consolidation and reconsolidation refer to transient neurobiological processes that are thought to implement changes in synaptic efficacy in neurons that participate in forming a memory, thereby over time stabilizing the memory and rendering it relatively permanent (or long-term). Consolidation follows initial memory acquisition, whereas reconsolidation follows reactivation of a memory that already has been consolidated, as during memory recall or retrieval.

  • Although most researchers studying the neuroscience of memory have embraced the concept of memory consolidation, reconsolidation was initially met with strong skepticism. The idea that long-term memory, regardless of its remoteness, can enter states of plasticity after reactivation, similar to the states observed shortly after acquisition, challenges the consolidation model, which proposes an irreversible memory-stabilization process that fixes memory permanently.

  • The concept that both consolidation and reconsolidation exist as time-dependent stabilization processes is deduced from structurally equivalent data sets by applying identical operant definitions and basic assumptions. These data sets show that amnesic treatments can affect memory only when they are applied shortly after memory acquisition (consolidation) or reactivation (reconsolidation), and that there is intact short-term but impaired long-term memory following the amnesic treatment.

  • Alternative explanations for the memory impairment that follows post-reactivation amnesic treatment have been proposed (for example, that the cause is treatment-induced lesions, transient retrieval blockade, facilitated extinction or new learning), but none of these interpretations can explain all of the available reactivation-induced memory-instability data (unlike the reconsolidation hypothesis itself). Furthermore, as reconsolidation and consolidation are deduced from very similar data sets using identical operant definitions, these interpretations also fall short of fully explaining results from consolidation studies.

  • Some argue that the existence of boundary conditions that moderate the occurrence of reconsolidation processes limits the validity rather than informing about the nature of reconsolidation. Therefore the criticism — based on the terminology — that reconsolidation should exactly recapitulate consolidation and occur for each and every memory is not justified.

  • The existing consolidation framework cannot accommodate the reconsolidation data. A new neurobiological model of memory is needed that acknowledges the long-held notion prominent in cognitive psychology that memory, at any age, is in essence plastic.

Abstract

Consolidated memories can re-enter states of transient instability following reactivation, from which they must again stabilize in order to persist, contradicting the previously dominant view that memory and its associated plasticity mechanisms progressively and irreversibly decline with time. We witness exciting times, as neuroscience begins embracing a position, long-held in cognitive psychology, that recognizes memory as a principally dynamic process. In light of remaining controversy, we here establish that the same operational definitions and types of evidence underpin the deduction of both reconsolidation and consolidation, thus validating the extrapolation that post-retrieval memory plasticity reflects processes akin to those that stabilized the memory following acquisition.

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Figure 1: Principal properties of consolidation and reconsolidation accounted for by Lewis's memory model.
Figure 2: Representative data from studies reporting reconsolidation impairment.
Figure 3: Is post-reactivation amnesia a nonspecific effect?
Figure 4: Predictions made by alternative interpretations of the reconsolidation impairment compared with actual reconsolidation data.

References

  1. Duncan, C. P. The retroactive effect of electroconvulsive shock. J. Comp. Physiol. Psychol. 42, 32–44 (1949).

    CAS  PubMed  Google Scholar 

  2. White, N. M. & McDonald, R. J. Multiple parallel memory systems in the brain of the rat. Neurobiol. Learn. Mem. 77, 125–184 (2002).

    PubMed  Google Scholar 

  3. Davis, M. Neurobiology of fear responses: the role of the amygdala. J. Neuropsychiatry Clin. Neurosci. 9, 382–402 (1997).

    CAS  PubMed  Google Scholar 

  4. LeDoux, J. E. Emotion circuits in the brain. Annu. Rev. Neurosci. 23, 155–184 (2000).

    CAS  PubMed  Google Scholar 

  5. Maren, S. Neurobiology of Pavlovian fear conditioning. Annu. Rev. Neurosci. 24, 897–931 (2001).

    CAS  PubMed  Google Scholar 

  6. Morris, R. G. Episodic-like memory in animals: psychological criteria, neural mechanisms and the value of episodic-like tasks to investigate animal models of neurodegenerative disease. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356, 1453–1465 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Thompson, R. F. & Krupa, D. J. Organization of memory traces in the mammalian brain. Annu. Rev. Neurosci. 17, 519–549 (1994).

    CAS  PubMed  Google Scholar 

  8. Ebbinghaus, M. Über das Gedächtnis (Buehler, Leipzig, 1885).

    Google Scholar 

  9. Glickman, S. Perseverative neural processes and consolidation of the memory trace. Psychol. Bull. 58, 218–233 (1961).

    CAS  PubMed  Google Scholar 

  10. McGaugh, J. L. Time-dependent processes in memory storage. Science 153, 1351–1358 (1966).

    CAS  PubMed  Google Scholar 

  11. Pastalkova, E. et al. Storage of spatial information by the maintenance mechanism of LTP. Science 313, 1141–1144 (2006). This paper identified PKMζ as the only molecule currently known to maintain LTM.

    Article  CAS  PubMed  Google Scholar 

  12. Scoville, W. B. & Milner, B. Loss of recent memory after bilateral hippocampal lesions. J. Neurol. Psychiatry 20, 11–21 (1957).

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  14. Dudai, Y. The neurobiology of consolidations, or, how stable is the engram? Annu. Rev. Psychol. 55, 51–86 (2004).

    PubMed  Google Scholar 

  15. Kandel, E. R. The molecular biology of memory storage: a dialogue between genes and synapses. Science 294, 1030–1038 (2001).

    CAS  PubMed  Google Scholar 

  16. Flexner, L. B., Flexner, J. B. & Stellar, E. Memory and cerebral protein synthesis in mice as affected by graded amounts of puromycin. Exp. Neurol. 13, 264–272 (1965).

    CAS  PubMed  Google Scholar 

  17. Gordon, W. C. & Spear, N. E. Effect of reactivation of a previously acquired memory on the interaction between memories in the rat. J. Exp. Psychol. 99, 349–355 (1973).

    CAS  PubMed  Google Scholar 

  18. McGaugh, J. L. & Krivanek, J. A. Strychnine effects on discrimination learning in mice: effects of dose and time of administration. Physiol. Behav. 5, 1437–1442 (1970).

    CAS  PubMed  Google Scholar 

  19. Spear, N. & Mueller, C. in Memory Consolidation: Psychobiology of Cognition (eds Weingarten, H. & Parker, E.) 111–147 (Laurence Erlbaum Associates, London, 1984).

    Google Scholar 

  20. Goelet, P., Castellucci, V. F., Schacher, S. & Kandel, E. R. The long and short of long-term memory- a molecular framework. Nature 322, 419–422 (1986).

    CAS  PubMed  Google Scholar 

  21. McGaugh, J. L. Memory - a century of consolidation. Science 287, 248–251 (2000).

    CAS  PubMed  Google Scholar 

  22. Dudai, Y. & Morris, R. in Brain, Perception, Memory: Advances in Cognitive Sciences (ed. Bolhius, J.) 149–162 (Oxford Univ. Press, Oxford, 2000).

    Google Scholar 

  23. Davis, H. P. & Squire, L. R. Protein synthesis and memory. A review. Psychol. Bull. 96, 518–559 (1984).

    CAS  PubMed  Google Scholar 

  24. Klann, E. & Sweatt, J. D. Altered protein synthesis is a trigger for long-term memory formation. Neurobiol. Learn. Mem. 89, 247–259 (2007).

    PubMed  PubMed Central  Google Scholar 

  25. Guzowski, J. F. & McGaugh, J. L. Antisense oligodeoxynucleotide-mediated disruption of hippocampal cAMP response element binding protein levels impairs consolidation of memory for water maze training. Proc. Natl Acad. Sci. USA 94, 2693–2698 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Yin, J. C. P., Del Vecchio, M., Zhou, H. & Tully, T. CREB as a Memory Modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophilia. Cell 81, 107–115 (1995).

    CAS  PubMed  Google Scholar 

  27. Silva, A. J., Kogan, J. H., Frankland, P. W. & Kida, S. CREB and memory. Annu. Rev. Neurosci. 21, 127–148 (1998).

    CAS  PubMed  Google Scholar 

  28. McGaugh, J. L. The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu. Rev. Neurosci. 27, 1–28 (2004).

    CAS  PubMed  Google Scholar 

  29. Martin, S. J., Grimwood, P. D. & Morris, R. G. Synaptic plasticity and memory: an evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000).

    CAS  PubMed  Google Scholar 

  30. Malenka, R. C. & Nicoll, R. A. Long-term potentiation--a decade of progress? Science 285, 1870–1874 (1999).

    CAS  PubMed  Google Scholar 

  31. Milner, B., Squire, L. R. & Kandel, E. R. Cognitive neuroscience and the study of memory. Neuron 20, 445–468 (1998).

    CAS  PubMed  Google Scholar 

  32. Shors, T. J. & Matzel, L. D. Long-term potentiation: what's learning got to do with it? Behav. Brain Sci. 20, 597–614; discussion 614–655 (1997).

    CAS  PubMed  Google Scholar 

  33. Routtenberg, A. & Rekart, J. L. Post-translational protein modification as the substrate for long-lasting memory. Trends Neurosci. 28, 12–19 (2005).

    CAS  PubMed  Google Scholar 

  34. Schafe, G. E. & LeDoux, J. E. Memory consolidation of auditory pavlovian fear conditioning requires protein synthesis and protein kinase A in the amygdala. J. Neurosci. 20, RC96 (2000).

    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). Sparking widespread renewed interest in reconsolidation, this seminal paper provided the first analytical demonstration of the phenomenon. It used localized infusions of anisomycin into the LBA, the site that putatively mediates memory consolidation for auditory fear conditioning.

    CAS  PubMed  Google Scholar 

  36. Bozon, B., Davis, S. & Laroche, S. A requirement for the immediate early gene zif268 in reconsolidation of recognition memory after retrieval. Neuron 40, 695–701 (2003).

    CAS  PubMed  Google Scholar 

  37. Debiec, J., LeDoux, J. E. & Nader, K. Cellular and systems reconsolidation in the hippocampus. Neuron 36, 527–538 (2002).

    CAS  PubMed  Google Scholar 

  38. Kida, S. et al. CREB required for the stability of new and reactivated fear memories. Nature Neurosci. 5, 348–355 (2002).

    CAS  PubMed  Google Scholar 

  39. Lee, J. L., Everitt, B. J. & Thomas, K. L. Independent cellular processes for hippocampal memory consolidation and reconsolidation. Science 304, 839–843 (2004). This paper showed that the mechanisms that mediate consolidation and reconsolidation can be doubly dissociated, suggesting that the differences between consolidation and reconsolidation cannot be explained by use of asymmetric protocols.

    CAS  PubMed  Google Scholar 

  40. Sangha, S., Scheibenstock, A. & Lukowiak, K. Reconsolidation of a long-term memory in Lymnaea requires new protein and RNA synthesis and the soma of right pedal dorsal 1. J. Neurosci. 23, 8034–8040 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Walker, M. P., Brakefield, T., Hobson, J. A. & Stickgold, R. Dissociable stages of human memory consolidation and reconsolidation. Nature 425, 616–620 (2003). This paper was the first to demonstrate reconsolidation in humans in a procedural memory task. It showed that learning of a new motor sequence after reactivation of an old one reduces memory accuracy for the reactivated old sequence on a later test, and that this effect is dependent on reactivation.

    CAS  PubMed  Google Scholar 

  42. Child., F. M., Epstein, H. T., Kuzirian, A. M. & Alkon, D. L. Memory reconsolidation in Hermissenda. Biol. Bull. 205, 218–219 (2003).

    CAS  PubMed  Google Scholar 

  43. Bailey, C. H. & Chen, M. Morphological basis of long-term habituation and sensitization in Aplysia. Science 220, 91–93 (1983).

    CAS  PubMed  Google Scholar 

  44. Nader, K. Memory traces unbound. Trends Neurosci. 26, 65–72 (2003).

    CAS  PubMed  Google Scholar 

  45. Bailey, C. H. & Kandel, E. R. Structural changes accompanying memory storage. Annu. Rev. Physiol. 55, 397–426 (1993).

    CAS  PubMed  Google Scholar 

  46. Lee, S. H. et al. Synaptic protein degradation underlies destabilization of retrieved fear memory. Science 319, 1253–1256 (2008). This paper showed that proteins must be degraded in order to transform a reactivated memory from a fixed to a labile state, suggesting that after reactivation degraded proteins need to be replaced through protein synthesis or else the reactivated memory cannot be re-stabilized.

    CAS  PubMed  Google Scholar 

  47. Gordon, W. C. Susceptibility of a reactivated memory to the effects of strychnine: a time-dependent phenomenon. Physiol. Behav. 18, 95–99 (1977).

    CAS  PubMed  Google Scholar 

  48. Rodriguez, W. A., Horne, C. A. & Padilla, J. L. Effects of glucose and fructose on recently reactivated and recently acquired memories. Prog. Neuropsychopharmacol. Biol. Psychiatry 23, 1285–1317 (1999).

    CAS  PubMed  Google Scholar 

  49. Horne, C. A., Rodriguez, W. A., Wright, T. P. & Padilla, J. L. Time-dependent effects of fructose on the modulation of a reactivated memory. Prog. Neuropsychopharmacol. Biol. Psychiatry 21, 649–658 (1997).

    CAS  PubMed  Google Scholar 

  50. Rodriguez, W. A., Rodriguez, S. B., Phillips, M. Y. & Martinez, J. L. Jr. Post-reactivation cocaine administration facilitates later acquisition of an avoidance response in rats. Behav. Brain Res. 59, 125–129 (1993).

    CAS  PubMed  Google Scholar 

  51. Misanin, J. R., Miller, R. R. & Lewis, D. J. Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science 160, 203–204 (1968). This seminal paper provided the first description of the reconsolidation phenomenon but, for historical reasons, reconsolidation remained outside the mainstream literature until 2000.

    Google Scholar 

  52. Gordon, W. C. Similarities of recently acquired and reactivated memories in interference. Am. J. Psychol. 90, 231–242 (1977).

    Google Scholar 

  53. Spear, N. Retrieval of memory in animals. Psychol. Rev. 80, 163–194 (1973).

    Google Scholar 

  54. Lewis, D. J. Psychobiology of active and inactive memory. Psychol. Bull. 86, 1054–1083 (1979). This conceptual paper was one of the earliest theoretical attempts to explain both the consolidation and the reconsolidation data sets.

    CAS  PubMed  Google Scholar 

  55. Fonseca, R., Nagerl, U. V. & Bonhoeffer, T. Neuronal activity determines the protein synthesis dependence of long-term potentiation. Nature Neurosci. 9, 478–480 (2006). An elegant LTP study which found that administration of the protein synthesis inhibitor anisomycin after and only after reactivation of an already-potentiated pathway attenuated LTP, suggesting that reconsolidation effects are observed for LTP as well.

    CAS  PubMed  Google Scholar 

  56. Doyere, V., Debiec, J., Monfils, M. H., Schafe, G. E. & LeDoux, J. E. Synapse-specific reconsolidation of distinct fear memories in the lateral amygdala. Nature Neurosci. 10, 414–416 (2007). This paper was the first to demonstrate that blocking reconsolidation reverses learning-induced changes in field potentials.

    CAS  PubMed  Google Scholar 

  57. Miller, C. A. & Marshall, J. F. Molecular substrates for retrieval and reconsolidation of cocaine-associated contextual memory. Neuron 47, 873–884 (2005).

    CAS  PubMed  Google Scholar 

  58. Valjent, E. et al. Plasticity-associated gene Krox24/Zif268 is required for long-lasting behavioral effects of cocaine. J. Neurosci. 26, 4956–4960 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Rose, J. K. & Rankin, C. H. Blocking memory reconsolidation reverses memory-associated changes in glutamate receptor expression. J. Neurosci. 26, 11582–11587 (2006). This paper showed that blocking reconsolidation in nematodes reverses the molecular correlates of LTM to those of naive animals.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Lewis, D. J., Bregman, N. J. & Mahan, J. J. Jr. Cue-dependent amnesia in rats. J. Comp. Physiol. Psychol. 2, 243–247 (1972).

    Google Scholar 

  61. Dawson, R. G. & McGaugh, J. L. Electroconvulsive shock effects on a reactivated memory trace: further examination. Science 166, 525–527 (1969).

    CAS  PubMed  Google Scholar 

  62. Gold, P. E. & King, R. A. Amnesia: tests of the effect of delayed footshock-electroconvulsive shock pairings. Physiol. Behav. 8, 797–800 (1972).

    CAS  PubMed  Google Scholar 

  63. De Vietti, T. & Holiday, J. H. Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace: a replication. Psychon. Sci. 29, 137–138 (1972).

    Google Scholar 

  64. Miller, R. R. & Springer, A. D. Amnesia, consolidation, and retrieval. Psychol. Rev. 80, 69–79 (1973).

    CAS  PubMed  Google Scholar 

  65. Eisenberg, M., Kobilo, T., Berman, D. E. & Dudai, Y. Stability of retrieved memory: inverse correlation with trace dominance. Science 301, 1102–1104 (2003). This elegant study showed in two different species that consolidation of extinction learning for a memory could inhibit reconsolidation for this memory.

    CAS  PubMed  Google Scholar 

  66. Pederia, M. E. & Maldonado, H. Protein synthesis subserves reconsolidation or extinction depending on reminder duration. Neuron 38, 863–869 (2003).

    Google Scholar 

  67. Milekic, M. H. & Alberini, C. M. Temporally graded requirement for protein synthesis following memory reactivation. Neuron 36, 521–525 (2002).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Stollhoff, N., Menzel, R. & Eisenhardt, D. Spontaneous recovery from extinction depends on the reconsolidation of the acquisition memory in an appetitive learning paradigm in the honeybee (Apis mellifera). J. Neurosci. 25, 4485–4492 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  70. Duvarci, S., Mamou, C. B. & Nader, K. Extinction is not a sufficient condition to prevent fear memories from undergoing reconsolidation in the basolateral amygdala. Eur. J. Neurosci. 24, 249–260 (2006).

    PubMed  Google Scholar 

  71. Debiec, J., Doyere, V., Nader, K. & Ledoux, J. E. Directly reactivated, but not indirectly reactivated, memories undergo reconsolidation in the amygdala. Proc. Natl Acad. Sci. USA 103, 3428–3433 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 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).

    PubMed  PubMed Central  Google Scholar 

  73. Forcato, C., Argibay, P. F., Pedreira, M. E. & Maldonado, H. Human reconsolidation does not always occur when a memory is retrieved: the relevance of the reminder structure. Neurobiol. Learn. Mem. 91, 50–57 (2008).

    PubMed  Google Scholar 

  74. Pedreira, M. E., Perez-Cuesta, L. M. & Maldonado, H. Mismatch between what is expected and what actually occurs triggers memory reconsolidation or extinction. Learn. Mem. 11, 579–585 (2004).

    PubMed  PubMed Central  Google Scholar 

  75. Morris, R. G. et al. Memory reconsolidation: sensitivity of spatial memory to inhibition of protein synthesis in dorsal hippocampus during encoding and retrieval. Neuron 50, 479–489 (2006).

    CAS  PubMed  Google Scholar 

  76. Hupbach, A., Hardt, O., Gomez, R. & Nadel, L. The dynamics of memory: context-dependent updating. Learn. Mem. 15, 574–579 (2008). This paper demonstrated in humans that episodic memory reconsolidation depends on re-exposure to the spatial context in which the original learning occurred, suggesting that the spatial context is crucial for inducing reconsolidation in human episodic memory.

    PubMed  Google Scholar 

  77. Lee, J. L., Di Ciano, P., Thomas, K. L. & Everitt, B. J. Disrupting reconsolidation of drug memories reduces cocaine-seeking behavior. Neuron 47, 795–801 (2005).

    CAS  PubMed  Google Scholar 

  78. Pedreira, M. E., Perez-Cuesta, L. M. & Maldonado, H. Reactivation and reconsolidation of long-term memory in the crab Chasmagnathus: protein synthesis requirement and mediation by NMDA-type glutamatergic receptors. J. Neurosci. 22, 8305–8311 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Rudy, J. W., Biedenkapp, J. C., Moineau, J. & Bolding, K. Anisomycin and the reconsolidation hypothesis. Learn. Mem. 13, 1–3 (2006).

    CAS  PubMed  Google Scholar 

  80. Duvarci, S. & Nader, K. Characterization of fear memory reconsolidation. J. Neurosci. 24, 9269–9275 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Gordon, W. C. & Spear, N. E. The effects of strychnine on recently acquired and reactivated passive avoidance memories. Physiol. Behav. 10, 1071–1075 (1973).

    CAS  PubMed  Google Scholar 

  82. Power, A. E., Berlau, D. J., McGaugh, J. L. & Steward, O. Anisomycin infused into the hippocampus fails to block “reconsolidation” but impairs extinction: the role of re-exposure duration. Learn. Mem. 13, 27–34 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Fischer, A., Sananbenesi, F., Schrick, C., Spiess, J. & Radulovic, J. Distinct roles of hippocampal de novo protein synthesis and actin rearrangement in extinction of contextual fear. J. Neurosci. 24, 1962–1966 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Vianna, M. R., Szapiro, G., McGaugh, J. L., Medina, J. H. & Izquierdo, I. Retrieval of memory for fear-motivated training initiates extinction requiring protein synthesis in the rat hippocampus. Proc. Natl Acad. Sci. USA 98, 12251–12254 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. McGaugh, J. L. Memory reconsolidation hypothesis revived but restrained: theoretical comment on Biedenkapp and Rudy (2004). Behav. Neurosci. 118, 1140–1142 (2004).

    PubMed  Google Scholar 

  86. Prado-Alcala, R. A. et al. Amygdala or hippocampus inactivation after retrieval induces temporary memory deficit. Neurobiol. Learn. Mem. 86, 144–149 (2006).

    PubMed  Google Scholar 

  87. Anokhin, K. V., Tiunova, A. A. & Rose, S. P. Reminder effects - reconsolidation or retrieval deficit? Pharmacological dissection with protein synthesis inhibitors following reminder for a passive-avoidance task in young chicks. Eur. J. Neurosci. 15, 1759–1765 (2002).

    PubMed  Google Scholar 

  88. Cahill, L., McGaugh, J. L. & Weinberger, N. M. The neurobiology of learning and memory: some reminders to remember. Trends Neurosci. 24, 578–581 (2001).

    CAS  PubMed  Google Scholar 

  89. Squire, L. R. Lost forever or temporarily misplaced? The long debate about the nature of memory impairment. Learn. Mem. 13, 522–529 (2006).

    PubMed  Google Scholar 

  90. Nader, K. & Wang, S. H. Fading in. Learn. Mem. 13, 530–535 (2006).

    PubMed  Google Scholar 

  91. Gold, P. & King, R. Storage failure versus retrieval failure. Psychol. Rev. 81, 465–469 (1974).

    CAS  PubMed  Google Scholar 

  92. Miller, R. & Springer, A. Implications of recovery from experimental amnesia. Psychol. Rev. 81, 470–473 (1974).

    CAS  PubMed  Google Scholar 

  93. de Hoz, L., Martin, S. J. & Morris, R. G. Forgetting, reminding, and remembering: the retrieval of lost spatial memory. PLoS Biol. 2, 1233–1242 (2004).

    CAS  Google Scholar 

  94. Lattal, K. M. & Abel, T. Behavioral impairments caused by injections of the protein synthesis inhibitor anisomycin after contextual retrieval reverse with time. Proc. Natl Acad. Sci. USA 101, 4667–4672 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Bailey, C. H., Bartsch, D. & Kandel, E. R. Toward a molecular definition of long-term memory storage. Proc. Natl Acad. Sci. USA 93, 13445–13452 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  96. Fonseca, R., Nagerl, U. V., Morris, R. G. & Bonhoeffer, T. Competing for memory: hippocampal LTP under regimes of reduced protein synthesis. Neuron 44, 1011–1020 (2004).

    CAS  PubMed  Google Scholar 

  97. Riccio, D. C., Millin, P. M. & Bogart, A. R. Reconsolidation: a brief history, a retrieval view, and some recent issues. Learn. Mem. 13, 536–544 (2006).

    PubMed  Google Scholar 

  98. 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).

    PubMed  PubMed Central  Google Scholar 

  99. Tronson, N. C., Wiseman, S. L., Olausson, P. & Taylor, J. R. Bidirectional behavioral plasticity of memory reconsolidation depends on amygdalar protein kinase A. Nature Neurosci. 9, 167–169 (2006). This paper provided the first demonstration that, like new memories, reactivated old memories could be enhanced by activating a kinase signalling pathway, showing that reactivation-induced plasticity allows memory modulation.

    CAS  PubMed  Google Scholar 

  100. Pavlov, I. P. Conditioned Reflexes (Dover, New York, 1927).

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  102. Rescorla, R. A. in Contemporary Learning Theories (eds Mowrer, R. R. & Klein, S. B.) 119–155 (Lawrence Erlbaum Associates, Mahwah, New Jersey, 2000).

    Google Scholar 

  103. Myers, K. M. & Davis, M. Systems-level reconsolidation: reengagement of the hippocampus with memory reactivation. Neuron 36, 340–343 (2002).

    CAS  PubMed  Google Scholar 

  104. Merlo, E. & Romano, A. Memory extinction entails the inhibition of the transcription factor NF-κB. PLoS ONE 3, e3687 (2008).

    PubMed  PubMed Central  Google Scholar 

  105. Eisenhardt, D. & Menzel, R. Extinction learning, reconsolidation and the internal reinforcement hypothesis. Neurobiol. Learn. Mem. 87, 167–173 (2007).

    PubMed  Google Scholar 

  106. Dudai, Y. & Eisenberg, M. Rites of passage of the engram: reconsolidation and the lingering consolidation hypothesis. Neuron 44, 93–100 (2004).

    CAS  PubMed  Google Scholar 

  107. Alberini, C. M. Mechanisms of memory stabilization: are consolidation and reconsolidation similar or distinct processes? Trends Neurosci. 28, 51–56 (2005).

    CAS  PubMed  Google Scholar 

  108. Gordon, W. C. in Information Processing in Animals: Memory Mechanisms (eds Spear, N. E. & Kleim, J. A.) 319–339 (Erlbaum, Hillsdale, New Jersey, 1981).

    Google Scholar 

  109. Mactutus, C. F., Riccio, D. C. & Ferek, J. M. Retrograde amnesia for old (reactivated) memory: some anomalous characteristics. Science 204, 1319–1320 (1979).

    CAS  PubMed  Google Scholar 

  110. Riccio, D. C., Moody, E. W. & Millin, P. M. Reconsolidation reconsidered. Integr. Physiol. Behav. Sci. 37, 245–253 (2002).

    PubMed  Google Scholar 

  111. Miller, R. R. & Marlin, N. A. in Memory Consolidation: Psychobiology of Cognition (eds Weingartner, H. & Parker, E. S.) 85–109 (Lawrence Erlbaum Associates, Hillsdale, New Jersey, 1984).

    Google Scholar 

  112. Sara, S. J. Retrieval and reconsolidation: toward a neurobiology of remembering. Learn. Mem. 7, 73–84 (2000).

    CAS  PubMed  Google Scholar 

  113. Nader, K., Hardt, O. & Wang, S. H. Response to Alberini: right answer, wrong question. Trends Neurosci. 28, 346–347 (2005).

    CAS  PubMed  Google Scholar 

  114. Blair, H. T., Schafe, G. E., Bauer, E. P., Rodrigues, S. M. & LeDoux, J. E. Synaptic plasticity in the lateral amygdala: a cellular hypothesis of fear conditioning. Learn. Mem. 8, 229–242 (2001).

    CAS  PubMed  Google Scholar 

  115. Schafe, G. E., Nader, K., Blair, H. T. & LeDoux, J. E. Memory consolidation of Pavlovian fear conditioning: a cellular and molecular perspective. Trends Neurosci. 24, 540–546 (2001).

    CAS  PubMed  Google Scholar 

  116. von Hertzen, L. S. & Giese, K. P. Memory reconsolidation engages only a subset of immediate-early genes induced during consolidation. J. Neurosci. 25, 1935–1942 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Biedenkapp, J. C. & Rudy, J. W. Context memories and reactivation: constraints on the reconsolidation hypothesis. Behav. Neurosci. 118, 956–964 (2004).

    PubMed  Google Scholar 

  118. Lewis, D. J. & Bregman, N. J. Source of cues for cue-dependent amnesia in rats. J. Comp. Physiol. Psychol. 85, 421–426 (1973).

    CAS  PubMed  Google Scholar 

  119. Rescorla, R. A. Pavlovian conditioning and its proper control procedures. Psychol. Rev. 74, 71–80 (1967).

    CAS  PubMed  Google Scholar 

  120. Quartermain, D. & McEwen, B. S. Temporal characteristics of amnesia induced by protein synthesis inhibitor: determination by shock level. Nature 228, 677–678 (1970).

    CAS  PubMed  Google Scholar 

  121. Quartermain, D., McEwen, B. S. & Azmitia, E. C. Jr. Recovery of memory following amnesia in the rat and mouse. J. Comp. Physiol. Psychol. 79, 360–370 (1972).

    CAS  PubMed  Google Scholar 

  122. Serota, R. G. Acetoxycycloheximide and transient amnesia in the rat. Proc. Natl Acad. Sci. USA 68, 1249–1250 (1971).

    CAS  PubMed  PubMed Central  Google Scholar 

  123. Squire, L. R. & Barondes, S. H. Variable decay of memory and its recovery in cycloheximide-treated mice. Proc. Natl Acad. Sci. USA 69, 1416–1420 (1972).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Cooper, R. M. & Koppenaal, R. J. Suppression and recovery of a one-trial avoidance response after a single ECS. Psychon. Sci. 1, 303–304 (1964).

    Google Scholar 

  125. Kohlenberg, R. & Trabasso, T. O. M. Recovery of a conditioned emotional response after one or two electroconvulsive shocks. J. Comp. Physiol. Psychol. 65, 270–273 (1968).

    CAS  PubMed  Google Scholar 

  126. Young, A. G. & Galluscio, E. H. Recovery from ECS-produced amnesia. Psychon. Sci. 22, 149–151 (1971).

    Google Scholar 

  127. Berman, D. E. & Dudai, Y. Memory extinction, learning anew, and learning the new: dissociations in the molecular machinery of learning in cortex. Science 291, 2417–2419 (2001).

    CAS  PubMed  Google Scholar 

  128. Tronel, S., Milekic, M. H. & Alberini, C. M. Linking new information to a reactivated memory requires consolidation and not reconsolidation mechanisms. PLoS Biol. 3, e293 (2005). This paper is one of the first to study the functional role of reconsolidation. It showed that reconsolidation was not necessary for learning an additional association after an initial association had been acquired.

    PubMed  PubMed Central  Google Scholar 

  129. Lee, J. L. Memory reconsolidation mediates the strengthening of memories by additional learning. Nature Neurosci. 11, 1264–1266 (2008). This paper reported a functional difference between consolidation and reconsolidation, showing that strengthening an existing memory recruits reconsolidation but not consolidation mechanisms.

    CAS  PubMed  Google Scholar 

  130. Ben Mamou, C., Gamache, K. & Nader, K. NMDA receptors are critical for unleashing consolidated auditory fear memories. Nature Neurosci. 9, 1237–1239 (2006). The first paper to propose a framework that permits testing of the mechanisms that mediate transformation of a memory from a fixed to a labile state. It also showed that the mechanism that mediates freezing can be doubly dissociated from the mechanisms involved in initiating reconsolidation.

    CAS  PubMed  Google Scholar 

  131. Suzuki, A., Mukawa, T., Tsukagoshi, A., Frankland, P. W. & Kida, S. Activation of LVGCCs and CB1 receptors required for destabilization of reactivated contextual fear memories. Learn. Mem. 15, 426–433 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  132. Ling, D. S. et al. Protein kinase Mζ is necessary and sufficient for LTP maintenance. Nature Neurosci. 5, 295–296 (2002).

    CAS  PubMed  Google Scholar 

  133. Serrano, P. et al. PKMζ maintains spatial, instrumental, and classically conditioned long-term memories. PLoS Biol. 6, e318 (2008).

    PubMed Central  Google Scholar 

  134. Lattal, K. M. & Abel, T. Different requirements for protein synthesis in acquisition and extinction of spatial preferences and context-evoked fear. J. Neurosci. 21, 5773–5780 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Cammarota, M., Bevilaqua, L. R., Medina, J. H. & Izquierdo, I. Retrieval does not induce reconsolidation of inhibitory avoidance memory. Learn. Mem. 11, 572–578 (2004).

    PubMed  PubMed Central  Google Scholar 

  136. Torras-Garcia, M., Lelong, J., Tronel, S. & Sara, S. J. Reconsolidation after remembering an odor-reward association requires NMDA receptors. Learn. Mem. 12, 18–22 (2005).

    PubMed  PubMed Central  Google Scholar 

  137. Duvarci, S., Nader, K. & Ledoux, J. E. Activation of extracellular signal-regulated kinase-mitogen-activated protein kinase cascade in the amygdala is required for memory reconsolidation of auditory fear conditioning. Eur. J. Neurosci. 21, 283–289 (2005).

    PubMed  Google Scholar 

  138. Gruest, N., Richer, P. & Hars, B. Memory consolidation and reconsolidation in the rat pup require protein synthesis. J. Neurosci. 24, 10488–10492 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Taubenfeld, S. M., Milekic, M. H., Monti, B. & Alberini, C. M. The consolidation of new but not reactivated memory requires hippocampal C/EBPβ. Nature Neurosci. 4, 813–818 (2001).

    CAS  PubMed  Google Scholar 

  140. Wang, S. H., Ostlund, S. B., Nader, K. & Balleine, B. W. Consolidation and reconsolidation of incentive learning in the amygdala. J. Neurosci. 25, 830–835 (2005).

    PubMed  PubMed Central  Google Scholar 

  141. Kelly, A., Laroche, S. & Davis, S. Activation of mitogen-activated protein kinase/extracellular signal-regulated kinase in hippocampal circuitry is required for consolidation and reconsolidation of recognition memory. J. Neurosci. 23, 5354–5360 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

K.N. was supported by the Canadian Institutes of Health Research, the Natural Sciences and Engineering Research Council of Canada, the Canadian Foundation for Innovation and the Volkswagen, Alfred P. Sloan and EJLB Foundations; K.N. is a William Dawson chair and a E.W.R. Steacie Memorial Fellow; O.H. is supported by the Deutsche Forschungsgemeinschaft. We would like to thank the Fondation des Treilles for hosting us while we wrote this manuscript. We thank C. Rankin, P. Frankland, E. Balaban and J. LeDoux for their comments on this manuscript.

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  1. Psychology Department, McGill University, 1205 Doctor Penfield Avenue, Montreal, H3A 1B1, Quebec, Canada

    Karim Nader & Oliver Hardt

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Glossary

Fear conditioning

A Pavlovian conditioning paradigm in which an initially neutral stimulus (for example, a tone or the context in which the animals are conditioned) is paired with another stimulus that evokes pain or strong somatic discomfort (typically a footshock). After a single pairing the initially neutral stimulus will elicit a spectrum of fear-like or defensive responses.

Short-term memory

(STM). Transient memory for an experience that does not require synthesis of new proteins or RNA and that can be expressed immediately. Typically, STM duration ranges from immediately to a couple of hours after acquisition.

Long-term memory

(LTM). Relatively stable memory that develops over time and is assumed to be mediated by changes in synaptic efficacy. LTM depends on synthesis of new proteins and RNA. Typically it is tested one or more days after training, as it takes several hours to stabilize. Once stabilized it can last for the remainder of the animal's life.

Long-term potentiation

(LTP). Traditionally demonstrated in hippocampal slice preparations, LTP is a persistent (lasting hours to days) enhancement of synaptic efficacy. It is rapidly induced by short high-frequency (tetanic) stimulation of a synaptic pathway.

Long-term depression

(LTD). A persistent reduction of synaptic efficacy that can be induced by repeated low-frequency stimulation of a synaptic pathway. Maintenance of LTD might require de novo protein synthesis.

Post-reactivation short-term memory

(PR-STM). By analogy with STM, PR-STM refers to a transient state into which existing LTM enters after it has been reactivated. The initial studies on reconsolidation indicate that PR-STM does not require synthesis of new RNA or proteins.

Post-reactivation long-term memory

(PR-LTM). By analogy with LTM, PR-LTM refers to the period of stability that reactivated memory enters after completing reconsolidation.

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Nader, K., Hardt, O. A single standard for memory: the case for reconsolidation. Nat Rev Neurosci 10, 224–234 (2009). https://doi.org/10.1038/nrn2590

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