Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The hippocampal sharp wave–ripple in memory retrieval for immediate use and consolidation

Nature Reviews Neuroscience volume 19, pages 744–757 (2018)Cite this article

Subjects

Abstract

Various cognitive functions have long been known to require the hippocampus. Recently, progress has been made in identifying the hippocampal neural activity patterns that implement these functions. One such pattern is the sharp wave–ripple (SWR), an event associated with highly synchronous neural firing in the hippocampus and modulation of neural activity in distributed brain regions. Hippocampal spiking during SWRs can represent past or potential future experience, and SWR-related interventions can alter subsequent memory performance. These findings and others suggest that SWRs support both memory consolidation and memory retrieval for processes such as decision-making. In addition, studies have identified distinct types of SWR based on representational content, behavioural state and physiological features. These various findings regarding SWRs suggest that different SWR types correspond to different cognitive functions, such as retrieval and consolidation. Here, we introduce another possibility — that a single SWR may support more than one cognitive function. Taking into account classic psychological theories and recent molecular results that suggest that retrieval and consolidation share mechanisms, we propose that the SWR mediates the retrieval of stored representations that can be utilized immediately by downstream circuits in decision-making, planning, recollection and/or imagination while simultaneously initiating memory consolidation processes.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Schematic of sharp wave–ripple rate across brain state and with movement speed.
Fig. 2: Schematic of possible local replays: in the forward and reverse directions, centrifugally and centripetally.
Fig. 3: Hypothesized function for sharp wave–ripples in retrieval of information from memory for immediate use and consolidation.

References

  1. Cohen, N. J. & Eichenbaum, H. Memory, Amnesia, and the Hippocampal System (MIT Press, 1993).

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

    CAS  PubMed  Google Scholar 

  3. Kandel, E. R., Dudai, Y. & Mayford, M. R. The molecular and systems biology of memory. Cell 157, 163–186 (2014).

    CAS  PubMed  Google Scholar 

  4. Schacter, D. L. Forgotten Ideas, Neglected Pioneers: Richard Semon and the Story of Memory (Taylor & Francis, 2012).

  5. Vanderwolf, C. H. Hippocampal electrical activity and voluntary movement in the rat. Electroencephalogr. Clin. Neurophysiol. 26, 407–418 (1969).

    CAS  PubMed  Google Scholar 

  6. O’Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Oxford Univ. Press, 1978).

  7. Kay, K. & Frank, L. M. Three brain states in the hippocampus and cortex. Hippocampus https://doi.org/10.1002/hipo.22956 (2018).

  8. Buzsaki, G. Hippocampal sharp wave-ripple: a cognitive biomarker for episodic memory and planning. Hippocampus 25, 1073–1188 (2015). This complete, in-depth review covers, among other topics, the physiology of the SWR and its potential functions in health and disease as well as a historical account of the discovery of replay.

    PubMed  PubMed Central  Google Scholar 

  9. Foster, D. J. Replay comes of age. Annu. Rev. Neurosci. 40, 581–602 (2017).

    CAS  PubMed  Google Scholar 

  10. Atherton, L. A., Dupret, D. & Mellor, J. R. Memory trace replay: the shaping of memory consolidation by neuromodulation. Trends Neurosci. 38, 560–570 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Tang, W. & Jadhav, S. P. Sharp-wave ripples as a signature of hippocampal-prefrontal reactivation for memory during sleep and waking states. Neurobiol. Learn. Mem. https://doi.org/10.1016/j.nlm.2018.01.002 (2018).

  12. Pfeiffer, B. E. The content of hippocampal “replay”. Hippocampus https://doi.org/10.1002/hipo.22824 (2017).

  13. Olafsdottir, H. F., Bush, D. & Barry, C. The role of hippocampal replay in memory and planning. Curr. Biol. 28, R37–R50 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Rothschild, G. The transformation of multi-sensory experiences into memories during sleep. Neurobiol. Learn. Mem. https://doi.org/10.1016/j.nlm.2018.03.019 (2018).

    Article  PubMed  Google Scholar 

  15. Carr, M. F., Jadhav, S. P. & Frank, L. M. Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nat. Neurosci. 14, 147–153 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Yu, J. Y. & Frank, L. M. Hippocampal-cortical interaction in decision making. Neurobiol. Learn. Mem. 117C, 34–41 (2015).

    Google Scholar 

  17. Girardeau, G. & Zugaro, M. Hippocampal ripples and memory consolidation. Curr. Opin. Neurobiol. 21, 452–459 (2011).

    CAS  PubMed  Google Scholar 

  18. Roumis, D. K. & Frank, L. M. Hippocampal sharp-wave ripples in waking and sleeping states. Curr. Opin. Neurobiol. 35, 6–12 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Squire, L. R. Mechanisms of memory. Science 232, 1612–1619 (1986).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Cohen, N. J., Poldrack, R. A. & Eichenbaum, H. Memory for items and memory for relations in the procedural/declarative memory framework. Memory 5, 131–178 (1997).

    CAS  PubMed  Google Scholar 

  22. Tulving, E. Episodic memory: from mind to brain. Annu. Rev. Psychol. 53, 1–25 (2002).

    PubMed  Google Scholar 

  23. Eichenbaum, H., Dudchenko, P., Wood, E., Shapiro, M. & Tanila, H. The hippocampus, memory, and place cells: is it spatial memory or a memory space? Neuron 23, 209–226 (1999).

    CAS  PubMed  Google Scholar 

  24. Wirth, S. et al. Single neurons in the monkey hippocampus and learning of new associations. Science 300, 1578–1581 (2003).

    CAS  PubMed  Google Scholar 

  25. Wirth, S. et al. Trial outcome and associative learning signals in the monkey hippocampus. Neuron 61, 930–940 (2009).

    Google Scholar 

  26. Rutishauser, U., Mamelak, A. N. & Schuman, E. M. Single-trial learning of novel stimuli by individual neurons of the human hippocampus-amygdala complex. Neuron 49, 805–813 (2006).

    CAS  PubMed  Google Scholar 

  27. Rutishauser, U., Ross, I. B., Mamelak, A. N. & Schuman, E. M. Human memory strength is predicted by theta-frequency phase-locking of single neurons. Nature 464, 903–907 (2010).

    CAS  PubMed  Google Scholar 

  28. Winson, J. Loss of hippocampal theta rhythm results in spatial memory deficit in the rat. Science 201, 160–163 (1978).

    CAS  PubMed  Google Scholar 

  29. Hasselmo, M. E., Bodelon, C. & Wyble, B. P. A proposed function for hippocampal theta rhythm: separate phases of encoding and retrieval enhance reversal of prior learning. Neural Comput. 14, 793–817 (2002).

    PubMed  Google Scholar 

  30. Spellman, T. et al. Hippocampal-prefrontal input supports spatial encoding in working memory. Nature 522, 309–314 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  32. Kim, J. J. & Fanselow, M. S. Modality-specific retrograde amnesia of fear. Science 256, 675–677 (1992).

    CAS  PubMed  Google Scholar 

  33. Dudai, Y. The restless engram: consolidations never end. Annu. Rev. Neurosci. 35, 227–247 (2012).

    CAS  PubMed  Google Scholar 

  34. Dudai, Y., Roediger, H. L. 3rd. & Tulving, E. in Science of Memory: Concepts (eds Dudai, Y., Roediger, H. L. 3rd. & Fitzpatrick, S. M.) 1–9 (Oxford Univ. Press, 2007). This book selects and defines memory concepts such as retrieval and consolidation. It argues that concept definitions are valuable to the study of memory because they enable communication between levels of study within neuroscience and across disciplines such as psychology and physiology and they identify elemental problems in the field.

  35. Dudai, Y. & Carruthers, M. The Janus face of Mnemosyne. Nature 434, 567 (2005).

    CAS  PubMed  Google Scholar 

  36. Morris, R. G., Garrud, P., Rawlins, J. N. & O’Keefe, J. Place navigation impaired in rats with hippocampal lesions. Nature 297, 681–683 (1982).

    CAS  PubMed  Google Scholar 

  37. Jutras, M. J. & Buffalo, E. A. Recognition memory signals in the macaque hippocampus. Proc. Natl Acad. Sci. USA 107, 401–406 (2010).

    CAS  PubMed  Google Scholar 

  38. Winocur, G., Moscovitch, M. & Bontempi, B. Memory formation and long-term retention in humans and animals: convergence towards a transformation account of hippocampal-neocortical interactions. Neuropsychologia 48, 2339–2356 (2010).

    PubMed  Google Scholar 

  39. Nadel, L., Samsonovich, A., Ryan, L. & Moscovitch, M. Multiple trace theory of human memory: computational, neuroimaging, and neuropsychological results. Hippocampus 10, 352–368 (2000).

    CAS  PubMed  Google Scholar 

  40. Hassabis, D., Kumaran, D. & Maguire, E. A. Using imagination to understand the neural basis of episodic memory. J. Neurosci. 27, 14365–14374 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Hassabis, D., Kumaran, D., Vann, S. D. & Maguire, E. A. Patients with hippocampal amnesia cannot imagine new experiences. Proc. Natl Acad. Sci. USA 104, 1726–1731 (2007).

    CAS  PubMed  Google Scholar 

  42. Schacter, D. L. et al. The future of memory: remembering, imagining, and the brain. Neuron 76, 677–694 (2012).

    CAS  PubMed  Google Scholar 

  43. Suzuki, W. A. & Eichenbaum, H. The neurophysiology of memory. Ann. NY Acad. Sci. 911, 175–191 (2000).

    CAS  PubMed  Google Scholar 

  44. Squire, L. R. & Zola-Morgan, S. The medial temporal lobe memory system. Science 253, 1380–1386 (1991).

    CAS  PubMed  Google Scholar 

  45. Riedel, G. et al. Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat. Neurosci. 2, 898–905 (1999).

    CAS  PubMed  Google Scholar 

  46. Anagnostaras, S. G., Maren, S. & Fanselow, M. S. Temporally graded retrograde amnesia of contextual fear after hippocampal damage in rats: within-subjects examination. J. Neurosci. 19, 1106–1114 (1999).

    CAS  PubMed  Google Scholar 

  47. Sekeres, M. J., Winocur, G. & Moscovitch, M. The hippocampus and related neocortical structures in memory transformation. Neurosci. Lett. 680, 39–53 (2018).

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  49. Dudai, Y., Karni, A. & Born, J. The consolidation and transformation of memory. Neuron 88, 20–32 (2015).

    CAS  PubMed  Google Scholar 

  50. Lisman, J., Cooper, K., Sehgal, M. & Silva, A. J. Memory formation depends on both synapse-specific modifications of synaptic strength and cell-specific increases in excitability. Nat. Neurosci. 21, 309–314 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Poo, M. M. et al. What is memory? The present state of the engram. BMC Biol. 14, 40 (2016).

    PubMed  PubMed Central  Google Scholar 

  52. Ben-Yakov, A., Dudai, Y. & Mayford, M. R. Memory retrieval in mice and men. Cold Spring Harb. Perspect. Biol. 7, a021790 (2015).

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  54. Squire, L. R., Genzel, L., Wixted, J. T. & Morris, R. G. Memory consolidation. Cold Spring Harb. Perspect. Biol. 7, a021766 (2015).

    PubMed  PubMed Central  Google Scholar 

  55. Sutherland, R. J. et al. Retrograde amnesia after hippocampal damage: recent versus remote memories in two tasks. Hippocampus 11, 27–42 (2001).

    CAS  PubMed  Google Scholar 

  56. Martin, S. J., de Hoz, L. & Morris, R. G. Retrograde amnesia: neither partial nor complete hippocampal lesions in rats result in preferential sparing of remote spatial memory, even after reminding. Neuropsychologia 43, 609–624 (2005).

    PubMed  Google Scholar 

  57. Born, J. & Wilhelm, I. System consolidation of memory during sleep. Psychol. Res. 76, 192–203 (2012).

    PubMed  Google Scholar 

  58. Josselyn, S. A. & Frankland, P. W. Memory allocation: mechanisms and function. Annu. Rev. Neurosci. 41, 389–413 (2018).

    CAS  PubMed  Google Scholar 

  59. Semon, R. W. Mnemic Psychology (George Allen & Unwin, 1923).

  60. Buzsaki, G., Leung, L. W. & Vanderwolf, C. H. Cellular bases of hippocampal EEG in the behaving rat. Brain Res. 287, 139–171 (1983).

    CAS  PubMed  Google Scholar 

  61. Buzsaki, G. Hippocampal sharp waves - their origin and significance. Brain Res. 398, 242–252 (1986).

    CAS  PubMed  Google Scholar 

  62. Sullivan, D. et al. Relationships between hippocampal sharp waves, ripples, and fast gamma oscillation: influence of dentate and entorhinal cortical activity. J. Neurosci. 31, 8605–8616 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Suzuki, S. S. & Smith, G. K. Spontaneous EEG spikes in the normal hippocampus. V. Effects of ether, urethane, pentobarbital, atropine, diazepam and bicuculline. Electroencephalogr. Clin. Neurophysiol. 70, 84–95 (1988).

    CAS  PubMed  Google Scholar 

  64. Ylinen, A. et al. Sharp wave-associated high-frequency oscillation (200 Hz) in the intact hippocampus: network and intracellular mechanisms. J. Neurosci. 15, 30–46 (1995).

    CAS  PubMed  Google Scholar 

  65. Oliva, A., Fernandez-Ruiz, A., Buzsaki, G. & Berenyi, A. Role of hippocampal CA2 region in triggering sharp-wave ripples. Neuron 91, 1342–1355 (2016).

    CAS  PubMed  Google Scholar 

  66. Sasaki, T. et al. Dentate network activity is necessary for spatial working memory by supporting CA3 sharp-wave ripple generation and prospective firing of CA3 neurons. Nat. Neurosci. 21, 258–269 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Amaral, D. G. & Witter, M. P. The three-dimensional organization of the hippocampal formation: a review of anatomical data. Neuroscience 31, 571–591 (1989).

    CAS  PubMed  Google Scholar 

  68. Li, X. G., Somogyi, P., Ylinen, A. & Buzsaki, G. The hippocampal CA3 network: an in vivo intracellular labeling study. J. Comp. Neurol. 339, 181–208 (1994).

    CAS  PubMed  Google Scholar 

  69. Valero, M. et al. Mechanisms for selective single-cell reactivation during offline sharp-wave ripples and their distortion by fast ripples. Neuron 94, 1234–1247.e7 (2017).

    CAS  PubMed  Google Scholar 

  70. Suzuki, S. S. & Smith, G. K. Spontaneous EEG spikes in the normal hippocampus. I. Behavioral correlates, laminar profiles and bilateral synchrony. Electroencephalogr. Clin. Neurophysiol. 67, 348–359 (1987).

    CAS  PubMed  Google Scholar 

  71. Jouvet, M., Michel, F. & Courjon, J. Electric activity of the rhinencephalon during sleep in cats. C. R. Seances Soc. Biol. Fil. 153, 101–105 (1959).

    CAS  PubMed  Google Scholar 

  72. Buzsaki, G., Horvath, Z., Urioste, R., Hetke, J. & Wise, K. High-frequency network oscillation in the hippocampus. Science 256, 1025–1027 (1992).

    CAS  PubMed  Google Scholar 

  73. English, D. F. et al. Excitation and inhibition compete to control spiking during hippocampal ripples: intracellular study in behaving mice. J. Neurosci. 34, 16509–16517 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Stark, E. et al. Pyramidal cell-interneuron interactions underlie hippocampal ripple oscillations. Neuron 83, 467–480 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Csicsvari, J., Hirase, H., Czurko, A., Mamiya, A. & Buzsaki, G. Fast network oscillations in the hippocampal CA1 region of the behaving rat. J. Neurosci. 19, RC20 (1999).

    CAS  PubMed  Google Scholar 

  76. Cheng, S. & Frank, L. M. New experiences enhance coordinated neural activity in the hippocampus. Neuron 57, 303–313 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Pfeiffer, B. E. & Foster, D. J. Hippocampal place-cell sequences depict future paths to remembered goals. Nature 497, 74–79 (2013). This compelling study identifies novel replay sequences starting from a rat’s current location and progressing towards a known goal location. This finding is one of the strongest pieces of evidence in support of a role for SWR replay in planning to guide immediately upcoming behaviour.

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Buzsaki, G. Two-stage model of memory trace formation: a role for “noisy” brain states. Neuroscience 31, 551–570 (1989).

    CAS  PubMed  Google Scholar 

  79. Thorndike, E. L. & Columbia, U. The Fundamentals of Learning. (Teachers College, Columbia Univ., 1932).

  80. Redish, A. D. Vicarious trial and error. Nat. Rev. Neurosci. 17, 147–159 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Papale, A. E., Zielinski, M. C., Frank, L. M., Jadhav, S. P. & Redish, A. D. Interplay between hippocampal sharp-wave-ripple events and vicarious trial and error behaviors in decision making. Neuron 92, 975–982 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  82. Speer, M. E., Bhanji, J. P. & Delgado, M. R. Savoring the past: positive memories evoke value representations in the striatum. Neuron 84, 847–856 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Wagner, U., Gais, S., Haider, H., Verleger, R. & Born, J. Sleep inspires insight. Nature 427, 352–355 (2004).

    CAS  PubMed  Google Scholar 

  84. O’Neill, J., Senior, T. & Csicsvari, J. Place-selective firing of CA1 pyramidal cells during sharp wave/ripple network patterns in exploratory behavior. Neuron 49, 143–155 (2006).

    PubMed  Google Scholar 

  85. Wang, D. V. et al. Mesopontine median raphe regulates hippocampal ripple oscillation and memory consolidation. Nat. Neurosci. 18, 728–735 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Vandecasteele, M. et al. Optogenetic activation of septal cholinergic neurons suppresses sharp wave ripples and enhances theta oscillations in the hippocampus. Proc. Natl Acad. Sci. USA 111, 13535–13540 (2014).

    CAS  PubMed  Google Scholar 

  87. Giovannini, M. G. et al. Effects of novelty and habituation on acetylcholine, GABA, and glutamate release from the frontal cortex and hippocampus of freely moving rats. Neuroscience 106, 43–53 (2001).

    CAS  PubMed  Google Scholar 

  88. Liu, Y., McAfee, S. S. & Heck, D. H. Hippocampal sharp-wave ripples in awake mice are entrained by respiration. Sci. Rep. 7, 8950 (2017).

    PubMed  PubMed Central  Google Scholar 

  89. O’Neill, J., Senior, T. J., Allen, K., Huxter, J. R. & Csicsvari, J. Reactivation of experience-dependent cell assembly patterns in the hippocampus. Nat. Neurosci. 11, 209–215 (2008).

    PubMed  Google Scholar 

  90. Karlsson, M. P. & Frank, L. M. Network dynamics underlying the formation of sparse, informative representations in the hippocampus. J. Neurosci. 28, 14271–14281 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Eschenko, O., Ramadan, W., Molle, M., Born, J. & Sara, S. J. Sustained increase in hippocampal sharp-wave ripple activity during slow-wave sleep after learning. Learn. Mem. 15, 222–228 (2008).

    PubMed  PubMed Central  Google Scholar 

  92. Jackson, J. C., Johnson, A. & Redish, A. D. Hippocampal sharp waves and reactivation during awake states depend on repeated sequential experience. J. Neurosci. 26, 12415–12426 (2006).

    CAS  PubMed  Google Scholar 

  93. Singer, A. C. & Frank, L. M. Rewarded outcomes enhance reactivation of experience in the hippocampus. Neuron 64, 910–921 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Foster, D. J. & Wilson, M. A. Reverse replay of behavioural sequences in hippocampal place cells during the awake state. Nature 440, 680–683 (2006). This study is the first description of reverse replay and is the first to propose that reverse replay functions in credit assignment.

    CAS  PubMed  Google Scholar 

  95. Marr, D. Simple memory: a theory for archicortex. Phil. Trans. R. Soc. Lond. B 262, 23–81 (1971).

    CAS  Google Scholar 

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

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  98. 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 

  99. Nakashiba, T., Buhl, D. L., McHugh, T. J. & Tonegawa, S. Hippocampal CA3 output is crucial for ripple-associated reactivation and consolidation of memory. Neuron 62, 781–787 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Novitskaya, Y., Sara, S. J., Logothetis, N. K. & Eschenko, O. Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation. Learn. Mem. 23, 238–248 (2016).

    PubMed  PubMed Central  Google Scholar 

  101. Girardeau, G., Cei, A. & Zugaro, M. Learning-induced plasticity regulates hippocampal sharp wave-ripple drive. J. Neurosci. 34, 5176–5183 (2014). This article provides the first demonstration that SWRs during post-experience sleep are necessary for a normal learning rate in a spatial memory task.

    PubMed  Google Scholar 

  102. Maingret, N., Girardeau, G., Todorova, R., Goutierre, M. & Zugaro, M. Hippocampo-cortical coupling mediates memory consolidation during sleep. Nat. Neurosci. 19, 959–964 (2016). This paper presents the first gain-of-function study of hippocampal–cortical coordination during the SWR. Electrical stimulation that enhanced the coordination between SWRs and cortical delta waves and spindles during post-experience sleep improved subsequent memory performance.

    CAS  PubMed  Google Scholar 

  103. Jadhav, S. P., Kemere, C., German, P. W. & Frank, L. M. Awake hippocampal sharp-wave ripples support spatial memory. Science 336, 1454–1458 (2012). This article presents the first study to demonstrate the necessity of awake SWRs in learning. It uses electrical stimulation to truncate SWRs during a spatial working memory task.

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Nokia, M. S., Mikkonen, J. E., Penttonen, M. & Wikgren, J. Disrupting neural activity related to awake-state sharp wave-ripple complexes prevents hippocampal learning. Front. Behav. Neurosci. 6, 84 (2012).

    PubMed  PubMed Central  Google Scholar 

  105. Jadhav, S. P. & Frank, L. M. in Time, Space and Memory in the Hippocampal Formation (eds Derdikman, D. & Knierim, J. J.) 351–371 (Space, 2014).

  106. Nokia, M. S., Penttonen, M. & Wikgren, J. Hippocampal ripple-contingent training accelerates trace eyeblink conditioning and retards extinction in rabbits. J. Neurosci. 30, 11486–11492 (2010).

    CAS  PubMed  Google Scholar 

  107. 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).

    PubMed  Google Scholar 

  108. Moser, M.-B., Rowland, D. C. & Moser, E. I. Place cells, grid cells, and memory. Cold Spring Harb. Perspect. Biol. 7, a021808 (2015).

    PubMed  PubMed Central  Google Scholar 

  109. Roux, L., Hu, B., Eichler, R., Stark, E. & Buzsaki, G. Sharp wave ripples during learning stabilize the hippocampal spatial map. Nat. Neurosci. 20, 845–853 (2017). This important study links awake SWR activity to learning in the form of place cell stabilization. Optogenetically silencing a subset of CA1 cells during awake SWRs led to place field remapping specifically for this subset.

    CAS  PubMed  PubMed Central  Google Scholar 

  110. van de Ven, G. M., Trouche, S., McNamara, C. G., Allen, K. & Dupret, D. Hippocampal offline reactivation consolidates recently formed cell assembly patterns during sharp wave-ripples. Neuron 92, 968–974 (2016).

    PubMed  PubMed Central  Google Scholar 

  111. Kovacs, K. A. et al. Optogenetically blocking sharp wave ripple events in sleep does not interfere with the formation of stable spatial representation in the CA1 area of the hippocampus. PLOS ONE 11, e0164675 (2016).

    PubMed  PubMed Central  Google Scholar 

  112. Sadowski, J. H., Jones, M. W. & Mellor, J. R. Sharp-wave ripples orchestrate the induction of synaptic plasticity during reactivation of place cell firing patterns in the hippocampus. Cell Rep. 14, 1916–1929 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  113. Behrens, C. J., van den Boom, L. P., de, H. L., Friedman, A. & Heinemann, U. Induction of sharp wave-ripple complexes in vitro and reorganization of hippocampal networks. Nat. Neurosci. 8, 1560–1567 (2005).

    CAS  PubMed  Google Scholar 

  114. Norimoto, H. et al. Hippocampal ripples down-regulate synapses. Science 359, 1524–1527 (2018). This study links in vivo SWR activity in mice to change at the synaptic level, reporting that optogenetic silencing of SWRs during sleep impairs learning and maintains synaptic weights that are otherwise observed to be downregulated.

    CAS  PubMed  Google Scholar 

  115. Lubenov, E. V. & Siapas, A. G. Decoupling through synchrony in neuronal circuits with propagation delays. Neuron 58, 118–131 (2008).

    CAS  PubMed  Google Scholar 

  116. Tononi, G. & Cirelli, C. Sleep function and synaptic homeostasis. Sleep Med. Rev. 10, 49–62 (2006).

    PubMed  Google Scholar 

  117. Tonegawa, S., Liu, X., Ramirez, S. & Redondo, R. Memory engram cells have come of age. Neuron 87, 918–931 (2015).

    CAS  PubMed  Google Scholar 

  118. Pavlides, C. & Winson, J. Influences of hippocampal place cell firing in the awake state on the activity of these cells during subsequent sleep episodes. J. Neurosci. 9, 2907–2918 (1989).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  120. Kudrimoti, H. S., Barnes, C. A. & McNaughton, B. L. Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics. J. Neurosci. 19, 4090–4101 (1999).

    CAS  PubMed  Google Scholar 

  121. 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). This elegant study finds that awake SWRs with activity specifically associated with goal locations predict subsequent memory performance and that this effect is dependent on the NMDA receptor.

    CAS  PubMed  PubMed Central  Google Scholar 

  122. Yu, J. Y. et al. Distinct hippocampal-cortical memory representations for experiences associated with movement versus immobility. eLife 6, e27621 (2017).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Karlsson, M. P. & Frank, L. M. Awake replay of remote experiences in the hippocampus. Nat. Neurosci. 12, 913–918 (2009). This study is the first to describe awake replay of remote experiences, which occurs just as frequently as local replay. It demonstrates that replay content is not necessarily triggered by specific sensory inputs in the local environment and introduces the possibility of a retrieval or awake consolidation function for the awake SWR.

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Gupta, A. S., van der Meer, M. A., Touretzky, D. S. & Redish, A. D. Hippocampal replay is not a simple function of experience. Neuron 65, 695–705 (2010). This article presents the first description of novel replay sequences. Replay of a part of the environment was more frequent when it had not been recently visited, demonstrating that replay is not a simple function of recent experience.

    CAS  PubMed  PubMed Central  Google Scholar 

  127. Davidson, T. J., Kloosterman, F. & Wilson, M. A. Hippocampal replay of extended experience. Neuron 63, 497–507 (2009). This study identifies extended replay sequences spanning multiple SWRs occurring in succession. It demonstrates that replay progresses at a characteristic speed and indicates chains of SWRs as a potential mechanism for the storage and use of extended experience.

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Wu, X. & Foster, D. J. Hippocampal replay captures the unique topological structure of a novel environment. J. Neurosci. 34, 6459–6469 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  129. Tang, W., Shin, J. D., Frank, L. M. & Jadhav, S. P. Hippocampal-prefrontal reactivation during learning is stronger in awake compared with sleep states. J. Neurosci. 37, 11789–11805 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  131. Jackson, J. & Redish, A. D. Network dynamics of hippocampal cell-assemblies resemble multiple spatial maps within single tasks. Hippocampus 17, 1209–1229 (2007).

    PubMed  Google Scholar 

  132. Olafsdottir, H. F., Carpenter, F. & Barry, C. Task demands predict a dynamic switch in the content of awake hippocampal replay. Neuron 96, 925–935.e6 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. McNaughton, B. L., Barnes, C. A. & O’Keefe, J. The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp. Brain Res. 52, 41–49 (1983).

    CAS  PubMed  Google Scholar 

  134. Frank, L. M., Stanley, G. B. & Brown, E. N. Hippocampal plasticity across multiple days of exposure to novel environments. J. Neurosci. 24, 7681–7689 (2004).

    CAS  PubMed  Google Scholar 

  135. Ambrose, R. E., Pfeiffer, B. E. & Foster, D. J. Reverse replay of hippocampal place cells is uniquely modulated by changing reward. Neuron 91, 1124–1136 (2016). This study finds modulation of SWR rate by reward that is accounted for specifically by modulation of reverse replay, indicating a functional difference between reverse and forward replay events. Specifically, this study suggests that reverse replay functions in credit assignment.

    CAS  PubMed  PubMed Central  Google Scholar 

  136. Clayton, N. S., Bussey, T. J. & Dickinson, A. Can animals recall the past and plan for the future? Nat. Rev. Neurosci. 4, 685–691 (2003).

    CAS  PubMed  Google Scholar 

  137. Panoz-Brown, D. et al. Replay of episodic memories in the rat. Curr. Biol. 28, 1628–1634.e7 (2018).

    CAS  PubMed  Google Scholar 

  138. Singer, A. C., Carr, M. F., Karlsson, M. P. & Frank, L. M. Hippocampal SWR activity predicts correct decisions during the initial learning of an alternation task. Neuron 77, 1163–1173 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  139. Wu, C. T., Haggerty, D., Kemere, C. & Ji, D. Hippocampal awake replay in fear memory retrieval. Nat. Neurosci. 20, 571–580 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Wikenheiser, A. M. & Redish, A. D. The balance of forward and backward hippocampal sequences shifts across behavioral states. Hippocampus 23, 22–29 (2013).

    PubMed  Google Scholar 

  141. Buckner, R. L. The role of the hippocampus in prediction and imagination. Annu. Rev. Psychol. 61, 27–48 (2010).

    PubMed  Google Scholar 

  142. Dragoi, G. & Tonegawa, S. Selection of preconfigured cell assemblies for representation of novel spatial experiences. Phil. Trans. R. Soc. B 369, 20120522 (2014).

    PubMed  Google Scholar 

  143. Dragoi, G. & Tonegawa, S. Preplay of future place cell sequences by hippocampal cellular assemblies. Nature 469, 397–401 (2011).

    CAS  PubMed  Google Scholar 

  144. Grosmark, A. D. & Buzsaki, G. Diversity in neural firing dynamics supports both rigid and learned hippocampal sequences. Science 351, 1440–1443 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Silva, D., Feng, T. & Foster, D. J. Trajectory events across hippocampal place cells require previous experience. Nat. Neurosci. 18, 1772–1779 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Schwindel, C. D. & McNaughton, B. L. Hippocampal-cortical interactions and the dynamics of memory trace reactivation. Prog. Brain Res. 193, 163–177 (2011).

    PubMed  Google Scholar 

  147. Rissman, J. & Wagner, A. D. Distributed representations in memory: insights from functional brain imaging. Annu. Rev. Psychol. 63, 101–128 (2012).

    PubMed  Google Scholar 

  148. Rajasethupathy, P. et al. Projections from neocortex mediate top-down control of memory retrieval. Nature 526, 653–659 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  150. Staresina, B. P. et al. Hierarchical nesting of slow oscillations, spindles and ripples in the human hippocampus during sleep. Nat. Neurosci. 18, 1679–1686 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  151. Penttonen, M., Kamondi, A., Sik, A., Acsady, L. & Buzsaki, G. Feed-forward and feed-back activation of the dentate gyrus in vivo during dentate spikes and sharp wave bursts. Hippocampus 7, 437–450 (1997).

    CAS  PubMed  Google Scholar 

  152. Bragin, A., Jando, G., Nadasdy, Z., van Landeghem, M. & Buzsaki, G. Dentate EEG spikes and associated interneuronal population bursts in the hippocampal hilar region of the rat. J. Neurophysiol. 73, 1691–1705 (1995).

    CAS  PubMed  Google Scholar 

  153. O’Neill, J., Boccara, C. N., Stella, F., Schoenenberger, P. & Csicsvari, J. Superficial layers of the medial entorhinal cortex replay independently of the hippocampus. Science 355, 184–188 (2017).

    PubMed  Google Scholar 

  154. Chrobak, J. J. & Buzsaki, G. Selective activation of deep layer (V-VI) retrohippocampal cortical neurons during hippocampal sharp waves in the behaving rat. J. Neurosci. 14, 6160–6170 (1994).

    CAS  PubMed  Google Scholar 

  155. Chrobak, J. J. & Buzsaki, G. High-frequency oscillations in the output networks of the hippocampal-entorhinal axis of the freely behaving rat. J. Neurosci. 16, 3056–3066 (1996).

    CAS  PubMed  Google Scholar 

  156. Olafsdottir, H. F., Carpenter, F. & Barry, C. Coordinated grid and place cell replay during rest. Nat. Neurosci. 19, 792–794 (2016).

    CAS  PubMed  Google Scholar 

  157. Chung, J. E. et al. A polymer probe-based system for high density, long-lasting electrophysiological recordings across distributed neuronal circuits. Preprint at bioRxiv https://doi.org/10.1101/242693 (2018).

    Article  Google Scholar 

  158. 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  PubMed  PubMed Central  Google Scholar 

  159. Jadhav, S. P., Rothschild, G., Roumis, D. K. & Frank, L. M. Coordinated excitation and inhibition of prefrontal ensembles during awake hippocampal sharp-wave ripple events. Neuron 90, 113–127 (2016). This study identifies a population of PFC neurons with firing rates modulated by awake SWRs. PFC neurons that increase firing rate tend to represent prior experience, whereas those that decrease firing rate are associated with the current location.

    CAS  PubMed  PubMed Central  Google Scholar 

  160. Remondes, M. & Wilson, M. A. Slow-gamma rhythms coordinate cingulate cortical responses to hippocampal sharp-wave ripples during wakefulness. Cell Rep. 13, 1327–1335 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  161. Wang, D. V. & Ikemoto, S. Coordinated interaction between hippocampal sharp-wave ripples and anterior cingulate unit activity. J. Neurosci. 36, 10663–10672 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  162. Rothschild, G., Eban, E. & Frank, L. M. A cortical-hippocampal-cortical loop of information processing during memory consolidation. Nat. Neurosci. 20, 251–259 (2017). This study identifies a cortical–hippocampal–cortical loop of information transmission during sleep. During sleep, delivering sounds that were associated during wake with traversal of specific spatial trajectories biases the content of activity in this loop.

    CAS  PubMed  Google Scholar 

  163. Wilber, A. A., Skelin, I., Wu, W. & McNaughton, B. L. Laminar organization of encoding and memory reactivation in the parietal cortex. Neuron 95, 1406–1419.e5 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. 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  PubMed  Google Scholar 

  165. 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).

    PubMed  PubMed Central  Google Scholar 

  166. Gomperts, S. N., Kloosterman, F. & Wilson, M. A. VTA neurons coordinate with the hippocampal reactivation of spatial experience. eLife 4, e05360 (2015).

    PubMed  PubMed Central  Google Scholar 

  167. Valdes, J. L., McNaughton, B. L. & Fellous, J. M. Offline reactivation of experience-dependent neuronal firing patterns in the rat ventral tegmental area. J. Neurophysiol. 114, 1183–1195 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  168. Khodagholy, D., Gelinas, J. N. & Buzsaki, G. Learning-enhanced coupling between ripple oscillations in association cortices and hippocampus. Science 358, 369–372 (2017). This study reports ripples in association cortex but not sensory cortex co-incident with hippocampal SWRs, with stronger coupling after learning. This study begins to address the question of which cortical areas, specifically, are involved in systems consolidation.

    CAS  PubMed  PubMed Central  Google Scholar 

  169. Ribeiro, S. et al. Long-lasting novelty-induced neuronal reverberation during slow-wave sleep in multiple forebrain areas. PLOS Biol. 2, E24 (2004).

    PubMed  PubMed Central  Google Scholar 

  170. Logothetis, N. K. et al. Hippocampal-cortical interaction during periods of subcortical silence. Nature 491, 547–553 (2012).

    CAS  PubMed  Google Scholar 

  171. Yu, J. Y., Liu, D. F., Loback, A., Grossrubatscher, I. & Frank, L. M. Specific hippocampal representations are linked to generalized cortical representations in memory. Preprint at bioRxiv https://doi.org/10.1101/207142 (2017).

    Article  Google Scholar 

  172. Battaglia, F. P., Sutherland, G. R. & McNaughton, B. L. Hippocampal sharp wave bursts coincide with neocortical “up-state” transitions. Learn. Mem. 11, 697–704 (2004).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  174. Isomura, Y. et al. Integration and segregation of activity in entorhinal-hippocampal subregions by neocortical slow oscillations. Neuron 52, 871–882 (2006).

    CAS  PubMed  Google Scholar 

  175. Peyrache, A., Khamassi, M., Benchenane, K., Wiener, S. I. & Battaglia, F. P. Replay of rule-learning related neural patterns in the prefrontal cortex during sleep. Nat. Neurosci. 12, 919–926 (2009).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  177. Teyler, T. J. & Rudy, J. W. The hippocampal indexing theory and episodic memory: updating the index. Hippocampus 17, 1158–1169 (2007).

    PubMed  Google Scholar 

  178. Kay, K. et al. A hippocampal network for spatial coding during immobility and sleep. Nature 531, 185–190 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  179. Colgin, L. L. Rhythms of the hippocampal network. Nat. Rev. Neurosci. 17, 239–249 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  180. Dragoi, G. & Buzsaki, G. Temporal encoding of place sequences by hippocampal cell assemblies. Neuron 50, 145–157 (2006).

    CAS  PubMed  Google Scholar 

  181. Wikenheiser, A. M. & Redish, A. D. Hippocampal theta sequences reflect current goals. Nat. Neurosci. 18, 289–294 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  182. Johnson, A. & Redish, A. D. Neural ensembles in CA3 transiently encode paths forward of the animal at a decision point. J. Neurosci. 27, 12176–12189 (2007).

    CAS  PubMed  Google Scholar 

  183. Wang, Y., Roth, Z. & Pastalkova, E. Synchronized excitability in a network enables generation of internal neuronal sequences. eLife 5, e20697 (2016).

    PubMed  PubMed Central  Google Scholar 

  184. Leonard, T. K. & Hoffman, K. L. Sharp-wave ripples in primates are enhanced near remembered visual objects. Curr. Biol. 27, 257–262 (2017).

    CAS  PubMed  Google Scholar 

  185. Patel, J., Schomburg, E. W., Berenyi, A., Fujisawa, S. & Buzsaki, G. Local generation and propagation of ripples along the septotemporal axis of the hippocampus. J. Neurosci. 33, 17029–17041 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  186. Aronov, D., Nevers, R. & Tank, D. W. Mapping of a non-spatial dimension by the hippocampal-entorhinal circuit. Nature 543, 719–722 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  187. Lisman, J. et al. Viewpoints: how the hippocampus contributes to memory, navigation and cognition. Nat. Neurosci. 20, 1434–1447 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  188. Ziv, Y. et al. Long-term dynamics of CA1 hippocampal place codes. Nat. Neurosci. 16, 264–266 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  189. Ramirez-Villegas, J. F., Logothetis, N. K. & Besserve, M. Diversity of sharp-wave-ripple LFP signatures reveals differentiated brain-wide dynamical events. Proc. Natl Acad. Sci. USA 112, E6379–E6387 (2015).

    CAS  PubMed  Google Scholar 

  190. Thorpe, S., Fize, D. & Marlot, C. Speed of processing in the human visual system. Nature 381, 520–522 (1996).

    CAS  PubMed  Google Scholar 

  191. Shadlen, M. N. & Shohamy, D. Decision making and sequential sampling from memory. Neuron 90, 927–939 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  192. Tse, D. et al. Schema-dependent gene activation and memory encoding in neocortex. Science 333, 891–895 (2011).

    CAS  PubMed  Google Scholar 

  193. Josselyn, S. A., Kohler, S. & Frankland, P. W. Heroes of the engram. J. Neurosci. 37, 4647–4657 (2017).

    CAS  PubMed  Google Scholar 

  194. O’Neill, J., Pleydell-Bouverie, B., Dupret, D. & Csicsvari, J. Play it again: reactivation of waking experience and memory. Trends Neurosci. 33, 220–229 (2010).

    PubMed  Google Scholar 

  195. Csicsvari, J., O’Neill, J., Allen, K. & Senior, T. Place-selective firing contributes to the reverse-order reactivation of CA1 pyramidal cells during sharp waves in open-field exploration. Eur. J. Neurosci. 26, 704–716 (2007).

    PubMed  PubMed Central  Google Scholar 

  196. Yamamoto, J. & Tonegawa, S. Direct medial entorhinal cortex input to hippocampal CA1 is crucial for extended quiet awake replay. Neuron 96, 217–227.e4 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  197. Valero, M. et al. Determinants of different deep and superficial CA1 pyramidal cell dynamics during sharp-wave ripples. Nat. Neurosci. 18, 1281–1290 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  198. Mishra, R. K., Kim, S., Guzman, S. J. & Jonas, P. Symmetric spike timing-dependent plasticity at CA3-CA3 synapses optimizes storage and recall in autoassociative networks. Nat. Commun. 7, 11552 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  199. Lopez, J., Gamache, K., Schneider, R. & Nader, K. Memory retrieval requires ongoing protein synthesis and NMDA receptor activity-mediated AMPA receptor trafficking. J. Neurosci. 35, 2465–2475 (2015).

    CAS  PubMed  Google Scholar 

  200. Szapiro, G. et al. Molecular mechanisms of memory retrieval. Neurochem. Res. 27, 1491–1498 (2002).

    CAS  PubMed  Google Scholar 

  201. Dudai, Y. Reconsolidation: the advantage of being refocused. Curr. Opin. Neurobiol. 16, 174–178 (2006).

    CAS  PubMed  Google Scholar 

  202. 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).

    CAS  PubMed  Google Scholar 

  203. Nader, K. Reconsolidation and the dynamic nature of memory. Cold Spring Harb. Perspect. Biol. 7, a021782 (2015).

    PubMed  PubMed Central  Google Scholar 

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

    CAS  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  206. 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).

    CAS  PubMed  Google Scholar 

  207. Straube, B. An overview of the neuro-cognitive processes involved in the encoding, consolidation, and retrieval of true and false memories. Behav. Brain Funct. 8, 35 (2012).

    PubMed  PubMed Central  Google Scholar 

  208. Simons, J. S., Garrison, J. R. & Johnson, M. K. Brain mechanisms of reality monitoring. Trends Cogn. Sci. 21, 462–473 (2017).

    PubMed  Google Scholar 

  209. Redish, A. D. Beyond the Cognitive Map: From Place Cells to Episodic Memory (MIT Press, 1999).

  210. Ciliberti, D. & Kloosterman, F. Falcon: a highly flexible open-source software for closed-loop neuroscience. J. Neural Eng. 14, 045004 (2017).

    PubMed  Google Scholar 

  211. Deng, X., Liu, D. F., Karlsson, M. P., Frank, L. M. & Eden, U. T. Rapid classification of hippocampal replay content for real-time applications. J. Neurophysiol. 116, 2221–2235 (2016).

    PubMed  PubMed Central  Google Scholar 

  212. Kanamori, N. A spindle-like wave in the cat hippocampus: a novel vigilance level-dependent electrical activity. Brain Res. 334, 180–182 (1985).

    CAS  PubMed  Google Scholar 

  213. Eguchi, K. & Satoh, T. Relationship between positive sharp wave bursts and unitary discharges in the cat hippocampus during slow wave sleep. Physiol. Behav. 40, 497–499 (1987).

    CAS  PubMed  Google Scholar 

  214. Ulanovsky, N. & Moss, C. F. Hippocampal cellular and network activity in freely moving echolocating bats. Nat. Neurosci. 10, 224–233 (2007).

    CAS  PubMed  Google Scholar 

  215. Skaggs, W. E. et al. EEG sharp waves and sparse ensemble unit activity in the macaque hippocampus. J. Neurophysiol. 98, 898–910 (2007).

    PubMed  Google Scholar 

  216. Leonard, T. K. et al. Sharp wave ripples during visual exploration in the primate hippocampus. J. Neurosci. 35, 14771–14782 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  217. Axmacher, N., Elger, C. E. & Fell, J. Ripples in the medial temporal lobe are relevant for human memory consolidation. Brain 131, 1806–1817 (2008).

    PubMed  Google Scholar 

  218. Le Van, Q. M. et al. Cell type-specific firing during ripple oscillations in the hippocampal formation of humans. J. Neurosci. 28, 6104–6110 (2008).

    Google Scholar 

  219. Bragin, A. et al. High-frequency oscillations in human brain. Hippocampus 9, 137–142 (1999). This study identifies a high-frequency oscillation in the EC and hippocampus of patients with epilepsy as a homologue of the SWR previously identified in rodents, introducing the possibility of their function also in human memory.

    CAS  PubMed  Google Scholar 

  220. Shein-Idelson, M., Ondracek, J. M., Liaw, H. P., Reiter, S. & Laurent, G. Slow waves, sharp waves, ripples, and REM in sleeping dragons. Science 352, 590–595 (2016).

    CAS  PubMed  Google Scholar 

  221. Vargas, R., Thorsteinsson, H. & Karlsson, K. A. Spontaneous neural activity of the anterodorsal lobe and entopeduncular nucleus in adult zebrafish: a putative homologue of hippocampal sharp waves. Behav. Brain Res. 229, 10–20 (2012).

    CAS  PubMed  Google Scholar 

  222. Staba, R. J. et al. High-frequency oscillations recorded in human medial temporal lobe during sleep. Ann. Neurol. 56, 108–115 (2004).

    PubMed  Google Scholar 

  223. Clemens, Z. et al. Temporal coupling of parahippocampal ripples, sleep spindles and slow oscillations in humans. Brain 130, 2868–2878 (2007).

    PubMed  Google Scholar 

  224. Logothetis, N. K. Neural-event-triggered fMRI of large-scale neural networks. Curr. Opin. Neurobiol. 31, 214–222 (2015). This study uses ripple-triggered fMRI in monkeys to demonstrate the broad activation of cortical areas and suppression of subcortical areas during the SWR.

    CAS  PubMed  Google Scholar 

  225. Kaplan, R. et al. Hippocampal sharp-wave ripples influence selective activation of the default mode network. Curr. Biol. 26, 686–691 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  226. Buzsaki, G. & Moser, E. I. Memory, navigation and theta rhythm in the hippocampal-entorhinal system. Nat. Neurosci. 16, 130–138 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  227. Yartsev, M. M. The emperor’s new wardrobe: rebalancing diversity of animal models in neuroscience research. Science 358, 466–469 (2017).

    CAS  PubMed  Google Scholar 

  228. Talakoub, O., Gomez Palacio Schjetnan, A., Valiante, T. A., Popovic, M. R. & Hoffman, K. L. Closed-loop interruption of hippocampal ripples through fornix stimulation in the non-human primate. Brain Stimul. 9, 911–918 (2016).

    PubMed  Google Scholar 

  229. Palop, J. J. & Mucke, L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat. Rev. Neurosci. 17, 777–792 (2016).

    CAS  PubMed  Google Scholar 

  230. Alvarado-Rojas, C. et al. Different mechanisms of ripple-like oscillations in the human epileptic subiculum. Ann. Neurol. 77, 281–290 (2015).

    PubMed  Google Scholar 

  231. Bragin, A., Mody, I., Wilson, C. L. & Engel, J. Jr. Local generation of fast ripples in epileptic brain. J. Neurosci. 22, 2012–2021 (2002).

    CAS  PubMed  Google Scholar 

  232. Gillespie, A. K. et al. Apolipoprotein E4 causes age-dependent disruption of slow gamma oscillations during hippocampal sharp-wave ripples. Neuron 90, 740–751 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  233. Witton, J. et al. Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia. J. Physiol. 594, 4615–4630 (2014).

    Google Scholar 

  234. Altimus, C., Harrold, J., Jaaro-Peled, H., Sawa, A. & Foster, D. J. Disordered ripples are a common feature of genetically distinct mouse models relevant to schizophrenia. Mol. Neuropsychiatry 1, 52–59 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  235. Wiegand, J. P. et al. Age is associated with reduced sharp-wave ripple frequency and altered patterns of neuronal variability. J. Neurosci. 36, 5650–5660 (2016).

    PubMed  PubMed Central  Google Scholar 

  236. Gerrard, J. L., Burke, S. N., McNaughton, B. L. & Barnes, C. A. Sequence reactivation in the hippocampus is impaired in aged rats. J. Neurosci. 28, 7883–7890 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  237. Ul Haq, R. et al. Pretreatment with beta-adrenergic receptor agonists facilitates induction of LTP and sharp wave ripple complexes in rodent hippocampus. Hippocampus 26, 1486–1492 (2016).

    CAS  PubMed  Google Scholar 

  238. Ishikawa, D., Matsumoto, N., Sakaguchi, T., Matsuki, N. & Ikegaya, Y. Operant conditioning of synaptic and spiking activity patterns in single hippocampal neurons. J. Neurosci. 34, 5044–5053 (2014).

    PubMed  Google Scholar 

  239. Nicole, O. et al. Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation. Sci. Rep. 6, 22728 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  240. Ciupek, S. M., Cheng, J., Ali, Y. O., Lu, H. C. & Ji, D. Progressive functional impairments of hippocampal neurons in a tauopathy mouse model. J. Neurosci. 35, 8118–8131 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  241. Suh, J., Foster, D. J., Davoudi, H., Wilson, M. A. & Tonegawa, S. Impaired hippocampal ripple-associated replay in a mouse model of schizophrenia. Neuron 80, 484–493 (2013).

    CAS  PubMed  Google Scholar 

  242. Phillips, K. G. et al. Decoupling of sleep-dependent cortical and hippocampal interactions in a neurodevelopmental model of schizophrenia. Neuron 76, 526–533 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  243. Carr, M. F., Karlsson, M. P. & Frank, L. M. Transient slow gamma synchrony underlies hippocampal memory replay. Neuron 75, 700–713 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  244. Pfeiffer, B. E. & Foster, D. J. Autoassociative dynamics in the generation of sequences of hippocampal place cells. Science 349, 180–183 (2015).

    CAS  PubMed  Google Scholar 

  245. Iaccarino, H. F. et al. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 540, 230–235 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  246. French, R. M. Catastrophic forgetting in connectionist networks. Trends Cogn. Sci. 3, 128–135 (1999).

    CAS  PubMed  Google Scholar 

  247. Hasselmo, M. E. Avoiding catastrophic forgetting. Trends Cogn. Sci. 21, 407–408 (2017).

    PubMed  Google Scholar 

  248. McCloskey, M. & Cohen, N. J. in The Psychology of Learning and Motivation Vol. 24 (ed. Bower, G. H.) 109–165 (Academic Press, 1989).

  249. 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).

    CAS  PubMed  Google Scholar 

  250. Kumaran, D., Hassabis, D. & McClelland, J. L. What learning systems do intelligent agents need? Complementary learning systems theory updated. Trends Cogn. Sci. 20, 512–534 (2016).

    PubMed  Google Scholar 

  251. Hinton, G. E., Dayan, P., Frey, B. J. & Neal, R. M. The “wake-sleep” algorithm for unsupervised neural networks. Science 268, 1158–1161 (1995).

    CAS  PubMed  Google Scholar 

  252. Mnih, V. et al. Human-level control through deep reinforcement learning. Nature 518, 529–533 (2015).

    CAS  PubMed  Google Scholar 

  253. Schaul, T., Quan, J., Antonoglou, I. & Silver, D. Prioritized experience replay. Preprint at ArXiv http://adsabs.harvard.edu/abs/2015arXiv151105952S (2015).

  254. Pritzel, A. et al. Neural episodic control. Preprint at ArXiv http://adsabs.harvard.edu/abs/2017arXiv170301988P (2017).

  255. Blundell, C. et al. Model-free episodic control. Preprint at ArXiv http://adsabs.harvard.edu/abs/2016arXiv160604460B (2016).

Download references

Acknowledgements

The authors thank J. Andreas, A. E. Comrie, T. Davidson, J. Guidera, T. H. Joo, K. Kay, H. Liang, B. P. Nachman and all other members of the Frank Lab for helpful discussion and close reading of sections of this text. The authors apologize to those whose work was not cited because of limited space. This work was supported by National Institue of Mental Health (NIMH) award number F30MH115582 (H.R.J.), National Institute of General Medical Sciences Medical Scientist Training Program grant #T32GM007618 (H.R.J.), NIMH grant R01 MH10517 (L.M.F.) and the Howard Hughes Medical Institute (L.M.F.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Reviewer information

Nature Reviews Neuroscience thanks L. Colgin, L. Menendez de la Prida and the other anonymous reviewer for their contribution to the peer review of this work.

Author information

Authors and Affiliations

  1. Medical Scientist Training Program and Neuroscience Graduate Program, University of California–San Francisco, San Francisco, CA, USA

    Hannah R. Joo

  2. Kavli Institute for Fundamental Neuroscience, Center for Integrative Neuroscience and Department of Physiology, University of California–San Francisco, San Francisco, CA, USA

    Hannah R. Joo & Loren M. Frank

  3. Howard Hughes Medical Institute, Chevy Chase, MD, USA

    Loren M. Frank

Authors
  1. Hannah R. Joo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Loren M. Frank
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

The authors both researched data for the article, provided substantial contribution to discussion of its content, wrote the article, and reviewed and edited the manuscript before submission.

Corresponding authors

Correspondence to Hannah R. Joo or Loren M. Frank.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Retrograde amnesia

An inability to access previously formed memories.

Anterograde amnesia

An inability to form new memories.

Fear conditioning

The process by which an animal learns to associate a cue (cued fear conditioning) or environment (contextual fear conditioning) with a negative outcome, such as a foot shock, and as a result expresses fear in response to the cue or environment alone.

Recollection

The conscious recall of a past experience.

Stimulus–response association

A conditioned relationship that supports an organism executing an action (the response) in reaction to a stimulus.

Planning

The process of setting future goals and determining the actions required to accomplish them, such as predetermining a route to a target location.

Imagination

The possibly subconscious mental act of considering possible future or alternative scenarios.

Local field potential

(LFP). The electrical potential measured by an extracellular electrode that results from the summed membrane currents of nearby neurons.

Rapid eye movement (REM) sleep

The ‘paradoxical’, wake-like phase of sleep that is marked by reduced synchrony in the LFP and REM and that is associated in humans with dreaming.

Slow-wave sleep

The phase of sleep marked by low-frequency oscillations in the LFP that is strongly associated with memory consolidation.

Trace eyeblink conditioning

A hippocampus-dependent classical conditioning task in which a conditioned stimulus such as a tone or flash of light is followed, after a delay, by a blink-inducing unconditioned stimulus, such as a corneal air puff.

Extinction

A behaviourally defined loss of a previously learned association, typically thought to require new learning.

Place fields

A place field is the location in an environment where a given cell increases its rate of action potential firing when the animal is in that location.

Place cells

Pyramidal cells of the hippocampus that fire action potentials at a higher rate when the animal is in a particular location in an environment.

NMDA receptor-mediated AMPA receptor trafficking

The process by which glutamatergic NMDA receptor activation leads to preparation of glutamatergic AMPA receptors for insertion in the membrane to result in increased synaptic weight.

Rights and permissions

Reprints and Permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Joo, H.R., Frank, L.M. The hippocampal sharp wave–ripple in memory retrieval for immediate use and consolidation. Nat Rev Neurosci 19, 744–757 (2018). https://doi.org/10.1038/s41583-018-0077-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41583-018-0077-1

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing