Labile or stable: opposing consequences for memory when reactivated during waking and sleep


Memory consolidation is a dynamic process. Reconsolidation theory assumes that reactivation during wakefulness transiently destabilizes memories, requiring them to reconsolidate in order to persist. Memory reactivation also occurs during slow-wave sleep (SWS) and is assumed to underlie the consolidating effect of sleep. Here, we tested whether the same principle of transient destabilization applies to memory reactivation during SWS. We reactivated memories in humans by presenting associated odor cues either during SWS or wakefulness. Reactivation was followed by an interference task to probe memory stability. As we expected, reactivation during waking destabilized memories. In contrast, reactivation during SWS immediately stabilized memories, thereby directly increasing their resistance to interference. Functional magnetic resonance imaging revealed that reactivation during SWS mainly activated hippocampal and posterior cortical regions, whereas reactivation during wakefulness primarily activated prefrontal cortical areas. Our results show that reactivation of memory serves distinct functions depending on the brain state of wakefulness or sleep.

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Figure 1: Experimental procedures and memory performance after odor reactivation.
Figure 2: Brain activity associated with odor-induced memory reactivation during wakefulness and sleep.


  1. 1

    Nader, K. & Hardt, O. A single standard for memory: the case for reconsolidation. Nat. Rev. Neurosci. 10, 224–234 (2009).

  2. 2

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

  3. 3

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

  4. 4

    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).

  5. 5

    Misanin, J.R., Miller, R.R. & Lewis, D.J. Retrograde amnesia produced by electroconvulsive shock after reactivation of a consolidated memory trace. Science 160, 554–555 (1968).

  6. 6

    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).

  7. 7

    Doyere, V., Debiec, J., Monfils, M.H., Schafe, G.E. & LeDoux, J.E. Synapse-specific reconsolidation of distinct fear memories in the lateral amygdala. Nat. Neurosci. 10, 414–416 (2007).

  8. 8

    Fonseca, R., Nagerl, U.V. & Bonhoeffer, T. Neuronal activity determines the protein synthesis dependence of long-term potentiation. Nat. Neurosci. 9, 478–480 (2006).

  9. 9

    Walker, M.P., Brakefield, T., Hobson, J.A. & Stickgold, R. Dissociable stages of human memory consolidation and reconsolidation. Nature 425, 616–620 (2003).

  10. 10

    Schiller, D. et al. Preventing the return of fear in humans using reconsolidation update mechanisms. Nature 463, 49–53 (2009).

  11. 11

    Kuhl, B.A., Shah, A.T., Dubrow, S. & Wagner, A.D. Resistance to forgetting associated with hippocampus-mediated reactivation during new learning. Nat. Neurosci. 13, 501–506 (2010).

  12. 12

    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).

  13. 13

    Forcato, C. et al. Reconsolidation of declarative memory in humans. Learn. Mem. 14, 295–303 (2007).

  14. 14

    Schwabe, L. & Wolf, O.T. New episodic learning interferes with the reconsolidation of autobiographical memories. PLoS ONE 4, e7519 (2009).

  15. 15

    Wilson, M.A. & McNaughton, B.L. Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994).

  16. 16

    Ji, D. & Wilson, M.A. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat. Neurosci. 10, 100–107 (2006).

  17. 17

    Euston, D.R., Tatsuno, M. & McNaughton, B.L. Fast-forward playback of recent memory sequences in prefrontal cortex during sleep. Science 318, 1147–1150 (2007).

  18. 18

    Peigneux, P. et al. Are spatial memories strengthened in the human hippocampus during slow wave sleep? Neuron 44, 535–545 (2004).

  19. 19

    Diekelmann, S. & Born, J. The memory function of sleep. Nat. Rev. Neurosci. 11, 114–126 (2010).

  20. 20

    Rasch, B., Buchel, C., Gais, S. & Born, J. Odor cues during slow-wave sleep prompt declarative memory consolidation. Science 315, 1426–1429 (2007).

  21. 21

    Rudoy, J.D., Voss, J.L., Westerberg, C.E. & Paller, K.A. Strengthening individual memories by reactivating them during sleep. Science 326, 1079 (2009).

  22. 22

    Rasch, B. & Born, J. Maintaining memories by reactivation. Curr. Opin. Neurobiol. 17, 698–703 (2007).

  23. 23

    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).

  24. 24

    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).

  25. 25

    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).

  26. 26

    Payne, J.D. et al. The role of sleep in false memory formation. Neurobiol. Learn. Mem. 92, 327–334 (2009).

  27. 27

    Simons, J.S. & Spiers, H.J. Prefrontal and medial temporal lobe interactions in long-term memory. Nat. Rev. Neurosci. 4, 637–648 (2003).

  28. 28

    Polyn, S.M. & Kahana, M.J. Memory search and the neural representation of context. Trends Cogn. Sci. 12, 24–30 (2008).

  29. 29

    Karpicke, J.D. & Roediger, H.L., III. The critical importance of retrieval for learning. Science 319, 966–968 (2008).

  30. 30

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

  31. 31

    Lee, J.L. Reconsolidation: maintaining memory relevance. Trends Neurosci. 32, 413–420 (2009).

  32. 32

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

  33. 33

    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 (2009).

  34. 34

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

  35. 35

    Petrides, M. Lateral prefrontal cortex: architectonic and functional organization. Phil. Trans. R. Soc. Lond. B 360, 781–795 (2005).

  36. 36

    Duncan, J. & Owen, A.M. Common regions of the human frontal lobe recruited by diverse cognitive demands. Trends Neurosci. 23, 475–483 (2000).

  37. 37

    Schacter, D.L. The seven sins of memory. Insights from psychology and cognitive neuroscience. Am. Psychol. 54, 182–203 (1999).

  38. 38

    Takashima, A. et al. Declarative memory consolidation in humans: a prospective functional magnetic resonance imaging study. Proc. Natl. Acad. Sci. USA 103, 756–761 (2006).

  39. 39

    Gais, S. et al. Sleep transforms the cerebral trace of declarative memories. Proc. Natl. Acad. Sci. USA 104, 18778–18783 (2007).

  40. 40

    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).

  41. 41

    Buzsáki, G. Memory consolidation during sleep: a neurophysiological perspective. J. Sleep Res. 7 Suppl 1: 17–23 (1998).

  42. 42

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

  43. 43

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

  44. 44

    Tse, D. et al. Schemas and memory consolidation. Science 316, 76–82 (2007).

  45. 45

    Huber, R., Ghilardi, M.F., Massimini, M. & Tononi, G. Local sleep and learning. Nature 430, 78–81 (2004).

  46. 46

    Stickgold, R. Of sleep, memories and trauma. Nat. Neurosci. 10, 540–542 (2007).

  47. 47

    Sobel, N. et al. Time course of odorant-induced activation in the human primary olfactory cortex. J. Neurophysiol. 83, 537–551 (2000).

  48. 48

    Rechtschaffen, A. & Kales, A. A Manual of Standardized Terminology, Techniques, and Scoring System for Sleep Stages of Human Subjects (US Department of Health, Education, and Welfare, National Institutes of Health, 1968).

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We thank I. Wilhelm for helpful discussions and J. Martens, F. Hobrack, M. Palm and K. Müller for assistance with data collection. This work was supported by grants from the Deutsche Forschungsgemeinschaft (SFB 654 and SFB TR 58).

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S.D., J.B. and B.R. designed the experiments and wrote the paper. S.D. and B.R. carried out the experiments and analyzed the data. C.B. provided analytic tools.

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Correspondence to Jan Born or Björn Rasch.

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The authors declare no competing financial interests.

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Supplementary Tables 1–5 and Supplementary Results (PDF 43 kb)

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Diekelmann, S., Büchel, C., Born, J. et al. Labile or stable: opposing consequences for memory when reactivated during waking and sleep. Nat Neurosci 14, 381–386 (2011).

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