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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

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).

  2. 2

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

  3. 3

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

  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).

  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).

  6. 6

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

  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).

  8. 8

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

  9. 9

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

  10. 10

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

  11. 11

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

  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).

  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).

  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).

  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).

  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).

  17. 17

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

  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).

  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).

  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).

  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).

  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).

  23. 23

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

  24. 24

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

  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).

  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).

  27. 27

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

  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).

  29. 29

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

  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).

  31. 31

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

  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).

  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).

  34. 34

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

  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).

Download references


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.

Correspondence to Daniel Bendor.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 (PDF 3385 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading