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Biasing the content of hippocampal replay during sleep


The hippocampus is essential for encoding self-experienced events into memory. During sleep, neural activity in the hippocampus related to a recent experience has been observed to spontaneously reoccur, and this 'replay' has been postulated to be important for memory consolidation. Task-related cues can enhance memory consolidation when presented during a post-training sleep session, and, if memories are consolidated by hippocampal replay, a specific enhancement for this replay should be observed. To test this, we trained rats on an auditory-spatial association task while recording from neuronal ensembles in the hippocampus. We found that, during sleep, a task-related auditory cue biased reactivation events toward replaying the spatial memory associated with that cue. These results indicate that sleep replay can be manipulated by external stimulation and provide further evidence for the role of hippocampal replay in memory consolidation.

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Figure 1: Behavioral task.
Figure 2: Hippocampal activity during behavior and sleep (rat 1, session 2).
Figure 3: Place cell responses during sleep reactivation events.
Figure 4: Rate bias during sleep reactivation events.
Figure 5: Rate bias during awake reactivation events.
Figure 6: Temporal dynamics of sound-evoked reactivation bias.
Figure 7: Bias in Bayesian decoded position during sleep reactivation events.


  1. 1

    Dupret, D., O'Neill, J., Pleydell-Bouverie, B. & Csicsvari, J. The reorganization and reactivation of hippocampal maps predict spatial memory performance. Nat. Neurosci. 13, 995–1002 (2010).

    CAS  Article  Google Scholar 

  2. 2

    Squire, L.R. Memory and the hippocampus: a synthesis from findings with rats, monkeys and humans. Psychol. Rev. 99, 195–231 (1992).

    CAS  Article  Google Scholar 

  3. 3

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

    Article  Google Scholar 

  4. 4

    Siapas, A.G. & Wilson, M.A. Coordinated interactions between hippocampal ripples and cortical spindles during slow-wave sleep. Neuron 21, 1123–1128 (1998).

    CAS  Article  Google Scholar 

  5. 5

    Sirota, A., Csicsvari, J., Buhl, D. & Buzsáki, G. Communication between neocortex and hippocampus during sleep in rodents. Proc. Natl. Acad. Sci. USA 100, 2065–2069 (2003).

    CAS  Article  Google Scholar 

  6. 6

    Walker, M.P. & Stickgold, R. Sleep-dependent learning and memory consolidation. Neuron 44, 121–133 (2004).

    CAS  Article  Google Scholar 

  7. 7

    Wierzynski, C.M., Lubenov, E.V., Gu, M. & Siapas, A.G. State-dependent spike-timing relationships between hippocampal and prefrontal circuits during sleep. Neuron 61, 587–596 (2009).

    CAS  Article  Google Scholar 

  8. 8

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

    CAS  Article  Google Scholar 

  9. 9

    Lee, A.K. & Wilson, M.A. Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36, 1183–1194 (2002).

    CAS  Article  Google Scholar 

  10. 10

    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 

  11. 11

    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 

  12. 12

    Girardeau, G., Benchenane, K., Wiener, S.I., Buzsáki, G. & Zugaro, M.B. Selective suppression of hippocampal ripples impairs spatial memory. Nat. Neurosci. 12, 1222–1223 (2009).

    CAS  Article  Google Scholar 

  13. 13

    Ego-Stengel, V. & Wilson, M.A. Disruption of ripple-associated hippocampal activity during rest impairs spatial learning in the rat. Hippocampus 20, 1–10 (2010).

    PubMed  PubMed Central  Google Scholar 

  14. 14

    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 

  15. 15

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

    CAS  Article  Google Scholar 

  16. 16

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

    CAS  Article  Google Scholar 

  17. 17

    Davidson, T.J., Kloosterman, F. & Wilson, M.A. Hippocampal replay of extended experience. Neuron 63, 497–507 (2009).

    CAS  Article  Google Scholar 

  18. 18

    O'Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 (1971).

    CAS  Article  Google Scholar 

  19. 19

    Moser, E.I., Kropff, E. & Moser, M.B. Place cells, grid cells and the brain's spatial representation system. Annu. Rev. Neurosci. 31, 69–89 (2008).

    CAS  Article  Google Scholar 

  20. 20

    Itskov, P.M., Vinnik, E., Honey, C., Schnupp, J.W. & Diamond, M.E. Sound sensitivity of neurons in rat hippocampus during performance of a sound-guided task. J. Neurophysiol. 107, 1822–1834 (2012).

    Article  Google Scholar 

  21. 21

    Zhang, K., Ginzburg, I., McNaughton, B.L. & Sejnowski, T.J. Interpreting neuronal population activity by reconstruction: unified framework with application to hippocampal place cells. J. Neurophysiol. 79, 1017–1044 (1998).

    CAS  Article  Google Scholar 

  22. 22

    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 

  23. 23

    Diba, K. & Buzsáki, G. Forward and reverse hippocampal place-cell sequences during ripples. Nat. Neurosci. 10, 1241–1242 (2007).

    CAS  Article  Google Scholar 

  24. 24

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

    CAS  Article  Google Scholar 

  25. 25

    Louie, K. & Wilson, M.A. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron 29, 145–156 (2001).

    CAS  Article  Google Scholar 

  26. 26

    Káli, S. & Dayan, P. Off-line replay maintains declarative memories in a model of hippocampal-neocortical interactions. Nat. Neurosci. 7, 286–294 (2004).

    Article  Google Scholar 

  27. 27

    Marshall, L., Helgadóttir, H., Mölle, M. & Born, J. Boosting slow oscillations during sleep potentiates memory. Nature 444, 610–613 (2006).

    CAS  Article  Google Scholar 

  28. 28

    Lesburguères, E. et al. Early tagging of cortical networks is required for the formation of enduring associative memory. Science 331, 924–928 (2011).

    Article  Google Scholar 

  29. 29

    Issa, E.B. & Wang, X. Sensory responses during sleep in primate primary and secondary auditory cortex. J. Neurosci. 28, 14467–14480 (2008).

    CAS  Article  Google Scholar 

  30. 30

    Schabus, M. et al. The fate of incoming stimuli during NREM sleep is determined by spindles and the phase of the slow oscillation. Front. Neurol. 3, 40 (2012).

    Article  Google Scholar 

  31. 31

    Plihal, W. & Born, J. Effects of early and late nocturnal sleep on priming and spatial memory. Psychophysiology 36, 571–582 (1999).

    CAS  Article  Google Scholar 

  32. 32

    Tahvildari, B., Fransén, E., Alonso, A.A. & Hasselmo, M.E. Switching between “On” and “Off” states of persistent activity in lateral entorhinal layer III neurons. Hippocampus 17, 257–263 (2007).

    Article  Google Scholar 

  33. 33

    Antony, J.W., Gobel, E.W., O'Hare, J.K., Reber, P.J. & Paller, K.A. Cued memory reactivation during sleep influences skill learning. Nat. Neurosci. 15, 1114–1116 (2012).

    CAS  Article  Google Scholar 

  34. 34

    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 

  35. 35

    Hirase, H., Leinekugel, X., Czurkó, A., Csicsvari, J. & Buzsáki, G. Firing rates of hippocampal neurons are preserved during subsequent sleep episodes and modified by novel awake experience. Proc. Natl. Acad. Sci. USA 98, 9386–9390 (2001).

    CAS  Article  Google Scholar 

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We thank M. Fee, H. Tanila and members of the Wilson laboratory for their helpful comments and suggestions. We would also like to thank C. Varela, J. Yamamoto, J. Siegle, E. Kuo, A. Hussain and E. Molina for technical assistance. This work was supported by a Merck Award/Helen Hay Whitney Postdoctoral Fellowship (D.B.), a Charles King Trust Postdoctoral Fellowship (D.B.), US National Institutes of Health grants 1-K99-DC012321-01 (D.B.) and 5R01MH061976 (M.A.W.).

Author information




D.B. designed the experiment, and collected and analyzed the data. D.B. and M.A.W. co-wrote the manuscript. M.A.W. supervised the experiment.

Corresponding author

Correspondence to Daniel Bendor.

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The authors declare no competing financial interests.

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Bendor, D., Wilson, M. Biasing the content of hippocampal replay during sleep. Nat Neurosci 15, 1439–1444 (2012).

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