Resistance to forgetting associated with hippocampus-mediated reactivation during new learning

Abstract

One of the reasons why we forget past experiences is because we acquire new memories in the interim. Although the hippocampus is thought to be important for acquiring and retaining memories, there is little evidence linking neural operations during new learning to the forgetting (or remembering) of earlier events. We found that, during the encoding of new memories, responses in the human hippocampus are predictive of the retention of memories for previously experienced, overlapping events. This brain-behavior relationship is evident in neural responses to individual events and in differences across individuals. We found that the hippocampus accomplishes this function by reactivating older memories as new memories are formed; in this case, reactivating neural responses that represented monetary rewards associated with older memories. These data reveal a fundamental mechanism by which the hippocampus tempers the forgetting of older memories as newer memories are acquired.

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Figure 1: Experimental design and behavioral results.
Figure 2: Relationship between AC encoding and AB forgetting.
Figure 3: Hippocampal responses during encoding and susceptibility to retroactive interference.
Figure 4: ROI analysis of reward-sensitive regions, as defined from independent reward-localizer task.

References

  1. 1

    Squire, L.R., Stark, C.E. & Clark, R.E. The medial temporal lobe. Annu. Rev. Neurosci. 27, 279–306 (2004).

    CAS  Article  Google Scholar 

  2. 2

    Eichenbaum, H. Hippocampus: cognitive processes and neural representations that underlie declarative memory. Neuron 44, 109–120 (2004).

    CAS  Article  Google Scholar 

  3. 3

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

    Article  Google Scholar 

  4. 4

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

    CAS  Article  Google Scholar 

  5. 5

    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  Google Scholar 

  6. 6

    Hupbach, A., Hardt, O., Gomez, R. & Nadel, L. The dynamics of memory: context-dependent updating. Learn. Mem. 15, 574–579 (2008).

    Article  Google Scholar 

  7. 7

    Müller, G.E. & Pilzecker, A. Experimentelle Beiträge zur Lehre vom Gedächtnis. Z. Psychol. Ergänzungsband 1, 1–300 (1900).

    Google Scholar 

  8. 8

    Barnes, J.M. & Underwood, B.J. Fate of first-list associations in transfer theory. J. Exp. Psychol. 58, 97–105 (1959).

    CAS  Article  Google Scholar 

  9. 9

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

    Article  Google Scholar 

  10. 10

    O'Reilly, R.C. & McClelland, J.L. Hippocampal conjunctive encoding, storage, and recall: avoiding a trade-off. Hippocampus 4, 661–682 (1994).

    CAS  Article  Google Scholar 

  11. 11

    Treves, A. & Rolls, E.T. Computational analysis of the role of the hippocampus in memory. Hippocampus 4, 374–391 (1994).

    CAS  Article  Google Scholar 

  12. 12

    Bakker, A., Kirwan, C.B., Miller, M. & Stark, C.E. Pattern separation in the human hippocampal CA3 and dentate gyrus. Science 319, 1640–1642 (2008).

    CAS  Article  Google Scholar 

  13. 13

    Kirwan, C.B. & Stark, C.E. Overcoming interference: an fMRI investigation of pattern separation in the medial temporal lobe. Learn. Mem. 14, 625–633 (2007).

    Article  Google Scholar 

  14. 14

    Leutgeb, J.K., Leutgeb, S., Moser, M.B. & Moser, E.I. Pattern separation in the dentate gyrus and CA3 of the hippocampus. Science 315, 961–966 (2007).

    CAS  Article  Google Scholar 

  15. 15

    Nakazawa, K. et al. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297, 211–218 (2002).

    CAS  Article  Google Scholar 

  16. 16

    Alvarez, P. & Squire, L.R. Memory consolidation and the medial temporal lobe: a simple network model. Proc. Natl. Acad. Sci. USA 91, 7041–7045 (1994).

    CAS  Article  Google Scholar 

  17. 17

    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  Google Scholar 

  18. 18

    Hoffman, K.L. & McNaughton, B.L. Coordinated reactivation of distributed memory traces in primate neocortex. Science 297, 2070–2073 (2002).

    CAS  Article  Google Scholar 

  19. 19

    Ji, D. & Wilson, M.A. Coordinated memory replay in the visual cortex and hippocampus during sleep. Nat. Neurosci. 10, 100–107 (2007).

    CAS  Article  Google Scholar 

  20. 20

    Sutherland, G.R. & McNaughton, B. Memory trace reactivation in hippocampal and neocortical neuronal ensembles. Curr. Opin. Neurobiol. 10, 180–186 (2000).

    CAS  Article  Google Scholar 

  21. 21

    Foster, D.J. & Wilson, M.A. Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature 440, 680–683 (2006).

    CAS  Article  Google Scholar 

  22. 22

    Karlsson, M.P. & Frank, L.M. Awake replay of remote experiences in the hippocampus. Nat. Neurosci. 12, 913–918 (2009).

    CAS  Article  Google Scholar 

  23. 23

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

    CAS  Article  Google Scholar 

  24. 24

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

    CAS  Article  Google Scholar 

  25. 25

    Knutson, B., Adams, C.M., Fong, G.W. & Hommer, D. Anticipation of increasing monetary reward selectively recruits nucleus accumbens. J. Neurosci. 21, RC159 (2001).

    CAS  Article  Google Scholar 

  26. 26

    Adcock, R.A., Thangavel, A., Whitfield-Gabrieli, S., Knutson, B. & Gabrieli, J.D. Reward-motivated learning: mesolimbic activation precedes memory formation. Neuron 50, 507–517 (2006).

    CAS  Article  Google Scholar 

  27. 27

    Wittmann, B.C. et al. Reward-related fMRI activation of dopaminergic midbrain is associated with enhanced hippocampus-dependent long-term memory formation. Neuron 45, 459–467 (2005).

    CAS  Article  Google Scholar 

  28. 28

    Brewer, J.B., Zhao, Z., Desmond, J.E., Glover, G.H. & Gabrieli, J.D. Making memories: brain activity that predicts how well visual experience will be remembered. Science 281, 1185–1187 (1998).

    CAS  Article  Google Scholar 

  29. 29

    Wagner, A.D. et al. Building memories: remembering and forgetting of verbal experiences as predicted by brain activity. Science 281, 1188–1191 (1998).

    CAS  Article  Google Scholar 

  30. 30

    Knutson, B. & Wimmer, G.E. Splitting the difference: how does the brain code reward episodes? Ann. NY Acad. Sci. 1104, 54–69 (2007).

    Article  Google Scholar 

  31. 31

    McClure, S.M., Laibson, D.I., Loewenstein, G. & Cohen, J.D. Separate neural systems value immediate and delayed monetary rewards. Science 306, 503–507 (2004).

    CAS  Article  Google Scholar 

  32. 32

    Lansink, C.S. et al. Preferential reactivation of motivationally relevant information in the ventral striatum. J. Neurosci. 28, 6372–6382 (2008).

    CAS  Article  Google Scholar 

  33. 33

    Pennartz, C.M. et al. The ventral striatum in off-line processing: ensemble reactivation during sleep and modulation by hippocampal ripples. J. Neurosci. 24, 6446–6456 (2004).

    CAS  Article  Google Scholar 

  34. 34

    Lansink, C.S., Goltstein, P.M., Lankelma, J.V., McNaughton, B.L. & Pennartz, C.M. Hippocampus leads ventral striatum in replay of place-reward information. PLoS Biol. 7, e1000173 (2009).

    Article  Google Scholar 

  35. 35

    Marshall, L. & Born, J. The contribution of sleep to hippocampus-dependent memory consolidation. Trends Cogn. Sci. 11, 442–450 (2007).

    Article  Google Scholar 

  36. 36

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

    CAS  Article  Google Scholar 

  37. 37

    Peigneux, P. et al. Offline persistence of memory-related cerebral activity during active wakefulness. PLoS Biol. 4, e100 (2006).

    Article  Google Scholar 

  38. 38

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

    CAS  Article  Google Scholar 

  39. 39

    Anderson, M.C. & McCulloch, K.C. Integration as a general boundary condition on retrieval-induced forgetting. J. Exp. Psychol. Learn. Mem. Cogn. 25, 608–629 (1999).

    Article  Google Scholar 

  40. 40

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

    CAS  Article  Google Scholar 

  41. 41

    Heckers, S., Zalesak, M., Weiss, A.P., Ditman, T. & Titone, D. Hippocampal activation during transitive inference in humans. Hippocampus 14, 153–162 (2004).

    Article  Google Scholar 

  42. 42

    Shohamy, D. & Wagner, A.D. Integrating memories in the human brain: hippocampal-midbrain encoding of overlapping events. Neuron 60, 378–389 (2008).

    CAS  Article  Google Scholar 

  43. 43

    Zalesak, M. & Heckers, S. The role of the hippocampus in transitive inference. Psychiatry Res. 172, 24–30 (2009).

    Article  Google Scholar 

  44. 44

    Kumaran, D., Summerfield, J.J., Hassabis, D. & Maguire, E.A. Tracking the emergence of conceptual knowledge during human decision making. Neuron 63, 889–901 (2009).

    CAS  Article  Google Scholar 

  45. 45

    O'Reilly, R.C. & Rudy, J.W. Computational principles of learning in the neocortex and hippocampus. Hippocampus 10, 389–397 (2000).

    CAS  Article  Google Scholar 

  46. 46

    Okado, Y. & Stark, C.E. Neural activity during encoding predicts false memories created by misinformation. Learn. Mem. 12, 3–11 (2005).

    Article  Google Scholar 

  47. 47

    Glover, G.H. & Law, C.S. Spiral-in/out BOLD fMRI for increased SNR and reduced susceptibility artifacts. Magn. Reson. Med. 46, 515–522 (2001).

    CAS  Article  Google Scholar 

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Acknowledgements

We thank B. Knutson, J. Cooper, G. Samanez-Larkin and S. McClure for helpful advice and discussions. This work was supported by the National Institute of Mental Health (5R01-MH080309) and the Alfred P. Sloan Foundation.

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Contributions

B.A.K. and A.D.W. designed the experiments and prepared the manuscript. B.A.K., A.T.S. and S.D. contributed to data collection and analysis.

Corresponding authors

Correspondence to Brice A Kuhl or Anthony D Wagner.

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The authors declare no competing financial interests.

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Supplementary Figures 1–5, Supplementary Tables 1–14 and Supplementary Results (PDF 5020 kb)

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Kuhl, B., Shah, A., DuBrow, S. et al. Resistance to forgetting associated with hippocampus-mediated reactivation during new learning. Nat Neurosci 13, 501–506 (2010). https://doi.org/10.1038/nn.2498

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