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  • Review Article
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Time cells in the hippocampus: a new dimension for mapping memories

Subjects

Key Points

  • Hippocampal time cells fire at successive moments in temporally structured experiences.

  • Temporal coding in the hippocampus is observed across a broad range of behavioural tasks and in different animal species and humans.

  • Time cells cannot be explained by variations in location or movement through space.

  • Time cells also encode spatial variables and other dimensions of specific events.

  • Time cells provide a mechanism for the temporal organization of episodic memories.

Abstract

Recent studies have revealed the existence of hippocampal neurons that fire at successive moments in temporally structured experiences. Several studies have shown that such temporal coding is not attributable to external events, specific behaviours or spatial dimensions of an experience. Instead, these cells represent the flow of time in specific memories and have therefore been dubbed 'time cells'. The firing properties of time cells parallel those of hippocampal place cells; time cells thus provide an additional dimension that is integrated with spatial mapping. The robust representation of both time and space in the hippocampus suggests a fundamental mechanism for organizing the elements of experience into coherent memories.

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Figure 1: Key features of time-cell firing sequences.
Figure 2: Early discoveries on temporal coding by hippocampal neurons.
Figure 3: Time coding and spatial coding.
Figure 4: Time cells have a role in memory.
Figure 5: The influence of temporal context on spatial coding.
Figure 6: Temporal context versus chaining models.

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References

  1. Tulving, E. Elements of Episodic Memory (Oxford Univ. Press,1983).

    Google Scholar 

  2. Templer, V. L. & Hampton, R. R. Episodic memory in non-human animals. Curr. Biol. 23, R801–R806 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Gallistel, C. R. & Balsam, P. D. Time to rethink the neural mechanisms of learning and memory. Neurobiol. Learn. Mem. 108, 136–144 (2014). This review proposes a reorientation of our views on learning away from the widely held view that learning is based on the temporal contiguity of associated events. Instead, the authors suggest that learning maps the temporal organization of sequential events.

    PubMed  Google Scholar 

  4. Eichenbaum, H. Memory on time. Trends Cogn. Sci. 17, 81–88 (2013).

    PubMed  PubMed Central  Google Scholar 

  5. Díaz-Mataix, L., Ruiz Martinez, R. C., Schafe, G. E., LeDoux, J. E. & Doyère, V. Detection of a temporal error trigger reconsoklidation of amygdala-dependent memories. Curr. Biol. 23, 467–472 (2013).

    PubMed  PubMed Central  Google Scholar 

  6. Berger, T. W., Rinaldi, P. C., Weisz, D. J. & Thompson, R. F. Single unit analysis of different hippocampal cell types during classical conditioning of the rabbit nictitating membrane response. J. Neurophysiol. 50, 1197–1219 (1983).

    CAS  PubMed  Google Scholar 

  7. McEchron, M. D., Tseng, W. & Disterhoft, J. F. Single neurons in CA1 hippocampus encode trace interval duration during trace heart rate (fear) conditioning in rabbit. J. Neurosci. 23, 1535–1547 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Jacobs, N. S., Allen, T. A., Nguyen, N. & Fortin, N. J. Critical role of the hippocampus in memory for elapsed time. J. Neurosci. 33, 13888–13893 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    Google Scholar 

  10. Buszaki, G. Time, space and memory. Nature 497, 568–569 (2013).

    Google Scholar 

  11. Rowland, D. C. & Moser, M.-B. Time finds its place in the hippocampus. Neuron 78, 953–954 (2013).

    CAS  PubMed  Google Scholar 

  12. Manns, J. R., Howard, M. & Eichenbaum, H. Gradual changes in hippocampal activity support remembering the order of events. Neuron 56, 530–540 (2007). This is the first experimental study to reveal a gradually changing representation of context by hippocampal neuronal ensembles that is linked to memory for the order of events in unique experiences.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Mankin, E. A. et al. Neuronal code for extended time in the hippocampus. Proc. Natl Acad. Sci. USA 109, 19462–19467 (2012).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  15. Rangel, L. M. et al. Temporlly selective contextual encoding in the dentate gyrus of the hippocampus. Nature Comm. http://dx.doi.org/10.1038/ncomms4181 (2014).

  16. Pastalkova, E., Itskov, V., Amarasingham, A. & Buzsáki, G. Internally generated cell assembly sequences in the rat hippocampus. Science 321, 1322–1327 (2008). This study revealed the existence of hippocampal neurons that fire briefly in sequence as rats run in a running wheel between alternations on a T-maze. Different firing sequences distinguished left-turn and right-turn paths through the maze.

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Gill, P. R., Mizumori, S. J. & Smith, D. M. Hippocampal episode fields develop with learning. Hippocampus 21, 1240–1249 (2011).

    PubMed  Google Scholar 

  18. MacDonald, C. J., Lepage, K. Q., Eden, U. T. & Eichenbaum, H. Hippocampal “time cells” bridge the gap in memory for discontiguous events. Neuron 71, 737–749 (2011). This study revealed the existence of time cells in animals performing a non-spatial task in which paired stimuli were separated by a delay. The authors showed that temporally specific firing patterns during the delay are not explained by variations in location or behaviour but are controlled by the critical temporal parameter of delay duration.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Kraus, B. J., Robinson, R. J. 2nd, White, J. A., Eichenbaum, H. & Hasselmo, M. E. Hippocampal 'time cells': time versus path integration. Neuron 78, 1090–1101 (2013). This study directly compares the coding of elapsed time, distance travelled and location by hippocampal neurons in rats during running in place on a treadmill. The results show that a combination of time and distance strongly determine the firing patterns of most neurons, with some encoding only time or only distance. Also, the same neurons that are time cells on the treadmill have clear place fields at locations outside the treadmill, showing that time cells and place cells are the same neurons.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. MacDonald, C. J., Carrow, S., Place, R. & Eichenbaum, H. Distinct hippocampal time cell sequences represent odor memories in immobilized rats. J. Neurosci. 33, 14607–14616 (2013). This study revealed that time cells fire in sequence during the delay period in head-fixed rats performing a delayed matching-to-sample task, showing that time-cell sequences exist even when movement is completely prevented. Furthermore, the results showed that distinct time-cell sequences are associated with different memories and that these sequences predict accurate memory performance.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Modi, M. N., Dhawale, A. K. & Bhalla, U. S. CA1 cell activity sequences emerge after reorganization of network correlation structure during associative learning. eLife 3, e01982 (2014). This study imaged calcium signals in hippocampal neurons of head-fixed mice during trace eye-blink classical conditioning. Hippocampal neural ensembles developed time-cell firing sequences, including during the trace period, associated with learning the conditioned response.

    PubMed  PubMed Central  Google Scholar 

  22. Naya, Y. & Suzuki, W. A. Integrating what and when across the primate medial temporal lobe. Science 333, 773–776 (2011). This study identifies time cells that fire as head-fixed monkeys learn the temporal order of pairs of visual stimuli separated by a delay. Notably, in this task, hippocampal neurons encoded elapsed time but not the visual stimuli, whereas neurons in upstream areas (entorhinal cortex, perirhinal cortex and inferotemporal cortex) progressively more strongly encoded information about the stimuli and less about elapsed time.

    CAS  PubMed  Google Scholar 

  23. Gelbard-Sagiv, H., Mukamel, R., Harel, M., Malach, R. & Fried, I. Internally generated reactivation of single neurons in human hippocampus during free recall. Science 322, 96–101 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Howard, M. W., Viskontas, I. V., Shankar, K. H. & Fried, I. Ensembles of human MTL neurons ''jump back in time'' in response to a repeated stimulus. Hippocampus 22, 1833–1847 (2012).

    PubMed  PubMed Central  Google Scholar 

  25. Paz, R. et al. A neural substrate in the human hippocampus for linking successive events. Proc. Natl Acad. Sci. USA 107, 6046–6051 (2010). This study revealed the emergence of a gradually changing representation of events with repeated exposures to specific film clips in humans. These patterns, similar to those observed in rats (reference 12), emerged only in the hippocampus and not in other medial temporal areas.

    CAS  PubMed  Google Scholar 

  26. Deadwyler, S. A., Bunn, T. & Hampson, R. E. Hippocampal ensemble activity during spatial delayed non-match to sample performance in rats. J. Neurosci. 16, 354–372 (1996).

    CAS  PubMed  Google Scholar 

  27. Shapiro, M. L., Tanila, H. & Eichenbaum, H. The cues that hippocampal place cells encode: dynamic and hierarchical representation of local and distal stimuli. Hippocampus 7, 624–642 (1997).

    CAS  PubMed  Google Scholar 

  28. Gothard, K. M., Skaggs, W. E., Moore, K. M. & McNaughton, B. L. Binding of hippocampal CA1 neural activity to multiple reference frames in a landmark-based navigation task. J. Neurosci. 16, 823–835 (1996).

    CAS  PubMed  Google Scholar 

  29. Ravassard, P. et al. Multisensory control of hippocampal spatiotemporal selectivity. Science 340, 1342–1346 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Komorowski, R. W., Manns, J. R. & Eichenbaum, H. Robust conjunctive item-place coding by hippocampal neurons parallels learning what happens. J. Neurosci. 29, 9918–9929 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Lenck-Santini, P. P, Fenton, A. A., & Muller, R. U. Discharge properties of hippocampal neurons during performance of a jump avoidance task. J. Neurosci. 28, 6773–6786 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  32. McKenzie, S. et al. Hippocampal representation of related and opposing memories develop within distinct, hierarchically-organized neural schemas. Neuron 83, 202–215 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Carr, M. F., Jadhav, S. P. & Frank, L. M. Hippocampal replay in the awake state: a potential substrate for memory consolidation and retrieval. Nature Neurosci. 14, 147–153 (2011). This paper reviews several studies showing that hippocampal place cells that fire in sequence along previously travelled routes also 'replay' their sequential firing patterns in compressed time during subsequent periods of quiet wakefulness.

    CAS  PubMed  Google Scholar 

  34. Jadhav, S. P., Kemere, C., German, P. W. & Frank, L. M. Awake hippocampal sharp-wave ripples support spatial memory. Science 336, 1454–1458 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Pfeiffer, B. E. & Foster, D. J. Hippocampal place cell sequences depict future paths to remembered goals. Nature 497, 74–79 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Frank, L. M., Brown, E. N. & Wilson, M. Trajectory encoding in the hippocampus and entorhinal cortex. Neuron 27, 169–178 (2000).

    CAS  PubMed  Google Scholar 

  38. Wood, E. R., Dudchenko, P., Robitsek, R. J. & Eichenbaum, H. Hippocampal neurons encode information about different types of memory episodes occurring in the same location. Neuron 27, 623–633 (2000).

    CAS  PubMed  Google Scholar 

  39. Shapiro, M. L., Kennedy, P. J. & Ferbinteanu, J. Representing episodes in the mammalian brain. Curr. Opin. Neurobiol. 16, 701–709 (2006). This paper reviews several studies showing that distinct ensembles of sequentially active hippocampal place cells map specific paths through a maze, including segments of paths that overlap. Thus, these ensembles represent the sequence of events that compose a specific route and not merely a set of adjacent locations in space.

    CAS  PubMed  Google Scholar 

  40. Ainge, J. A., Tamosiunaite, M., Woergoetter, F. & Dudchencko, P. A. Hippocampal CA1 place cells encode intended destination on a maze with multiple choice points. J. Neurosci. 27, 9769–9779 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Robitsek, R. J., White, J. & Eichenbaum, H. Place cell activation predicts subsequent memory. Behav. Brain Res. 254, 65–72 (2013).

    PubMed  PubMed Central  Google Scholar 

  42. Ginther, M. R., Walsh, D. F. & Ramus, S. J. Hippocampal neurons encode different episodes in an overlapping sequence of odors task. J. Neurosci. 31, 2706–2711 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Cabral, H. O. et al. Oscillatory dynamics and place field maps reflect hippocampal ensemble processing of sequence and place memory under NMDA receptor control. Neuron 81, 402–415 (2014). This study shows that hippocampal firing patterns can signal either a series of positions traversed or a sequence of actions, depending upon the current behavioural strategy. Thus hippocampal representations can either be anchored to space or driven by the temporal organization of memories.

    CAS  PubMed  Google Scholar 

  44. Gibbon, J., Malpani, C., Dale, C. L. & Gallistel, R. Toward a neurobiology of temporal cognition: advances and challenges. Curr. Opin. Neurobiol. 7, 170–184 (1997).

    CAS  PubMed  Google Scholar 

  45. Mauk, M. D. & Buonomano, D. V. The neural basis of temporal processing. Ann. Rev. Neurosci. 27, 307–340 (2004).

    CAS  PubMed  Google Scholar 

  46. Buhusi, C. V. & Meck, W. H. What makes us tick? Functional and neural mechanisms of interval timing. Nature Rev. Neurosci. 6, 755–765 (2005).

    CAS  Google Scholar 

  47. Yin, B. & Troger, A. B. Exploring the 4th dimension: hippocampus, time, and memory revisited. Front. Int. Neurosci. 5, 36 (2011).

    Google Scholar 

  48. Mattel, M. S. & Meck, W. H. Neuropsychological mechanisms of interval timing behavior. BioEssays 22, 94–103 (2000).

    Google Scholar 

  49. Lustig, C., Matell, M. S. & Meck, W. H. Not “just” a coincidence: frontal-striatal interactions in working memory and interval timing. Memory 13, 441–448 (2005).

    PubMed  Google Scholar 

  50. Kim. J., Ghim, J.-W., Lee, J. H., & Jung, M. W. Neural correlates of interval timing in the prefrontal cortex. J. Neurosci. 33, 13834–13847 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Leon, M. I. & Shadlen, M. N. Representation of time by neurons in the posterior parietal cortex of the macaque. Neuron 38, 317–327 (2003). This study identifies neurons in the lateral parietal cortex that alter their firing rates according to elapsed time in monkeys performing a task in which they matched elapsed time to a remembered standard interval.Information used in the perception of temporal intervals in cortical areas (and elsewhere) might be the source of time signals to the hippocampus.

    CAS  PubMed  Google Scholar 

  52. Janssen, P. & Shadlen, M. N. A representation of the hazard rate of elapsed time in macaque area LIP. Nature Neurosci. 8, 234–241 (2005).

    CAS  PubMed  Google Scholar 

  53. Davis, B., Christie, J. & Rorden, C. Temporal order judgments activate temporal parietal junction. J. Neurosci. 29, 3182–3188 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Watrous, A. J. et al. Frequency-specific network connectivity increases underlie accurate spatiotemporal memory retrieval. Nature Neurosci. 16, 349–356 (2013).

    CAS  PubMed  Google Scholar 

  55. Roberts, B. M., Hsieh, L.-T. & Ranganath, C. Oscillatory activity during maintenance of spatial and temporal information. Neuropsychologia 51, 349–357 (2013).

    PubMed  Google Scholar 

  56. Epstein, R. & Kanwisher, N. A cortical representation of the local visual environment. Nature 392, 598–601 (1998).

    CAS  PubMed  Google Scholar 

  57. Aminoff, E., Gronau, N. & Bar, M. The parahippocampal cortex mediates spatial and nonspatial associations. Cereb. Cortex 17, 1493–1503 (2007).

    CAS  PubMed  Google Scholar 

  58. Turk-Browne, N. B., Simon, M. G. & Sederberg, P. B. Scene representations in parahippocampal cortex depend on temporal context. J. Neurosci. 32, 7202–7207 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Hsieh, L. T., Gruber, M. J., Jenkins, L. J. & Ranganath, C. Hippocampal activity patterns carry information about objects in temporal context. Neuron 81, 1165–1178 (2014). This multivoxel pattern analysis of functional MRI scans in humans shows that activity patterns in the hippocampus carry information about the temporal positions of objects in learned sequences, whereas patterns in the parahippocampal cortex signal the temporal position only and patterns in the perirhinal cortex signalled object information only.

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Sauvage, M. M., Beer, Z., Ekovich, M., Ho, L. & Eichenbaum, H. The caudal medial entorhinal cortex: a selective role in recollection-based recognition memory. J. Neurosci. 30, 15695–15699 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Suh, J., Rivest, A. J., Nakashiba, T., Tominaga, T. & Tonegawa, S. Entorhinal cortex layer III input to the hippocampus is crucial for temporal association memory. Science 334, 1415–1412 (2011).

    CAS  PubMed  Google Scholar 

  62. Kitamura, T. et al. Island cells control temporal association memory. Science 343, 896–901 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  63. Kraus, B. J. et al. Grid cells are time cells. Soc. Neurosci. Abstr. 769.19 (2013).

  64. Howard, M. et al. A unified mathematical framework for coding time, space, and sequences in the medial temporal lobe. J. Neurosci. 34, 4692–4707 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  65. MacDonald, C. J. Prospective and retrospective duration memory in the hippocampus: is time in the foreground or background? Phil. Trans. R. Soc. B 369, 20120463 (2014).

    PubMed  Google Scholar 

  66. MacDonald, C. J., Fortin, N. J., Sakata, S. & Meck, W. H. Retrospective and prospective views on the role of the hippocampus in interval timing and memory for elapsed time. Timing Time Percept. 2, 51–61 (2014).

    Google Scholar 

  67. Mehta, M. R., Quirk, M. C. & Wilson, M. A. Experience-dependent asymmetric shape of hippocampal receptive fields. Neuron 25, 707–715 (2000).

    CAS  PubMed  Google Scholar 

  68. Itskov, V., Curto, C., Pastalkova, E. & Buzsáki, G. Cell assembly sequences arising from spike threshold adaptation keep track of time in the hippocampus. J. Neurosci. 31, 2828–2834 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Howard, M. W. & Eichenbaum, H. The hippocampus, time, and memory across scales. J. Exper. Psychol. General 142, 1211–1230 (2013).

    Google Scholar 

  70. 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 

  71. Cheng, J. & Ji, D. Rigid firing sequences undermine spatial memory codes in a neurodegenerative mouse model. eLife 2, e00647 (2013).

    PubMed  PubMed Central  Google Scholar 

  72. Wallenstein, G. V., Eichenbaum, H. & Hasselmo, M. E. The hippocampus as an associator of discontiguous events. Trends Neurosci. 21, 317–323 (1998).

    CAS  PubMed  Google Scholar 

  73. Kesner, R. P., Hunsaker, M. R. & Gilbert, P. E. The role of CA1 in the acquisition of an object-trace-odor paired associate task. Behav. Neurosci. 119, 781–786 (2005).

    PubMed  Google Scholar 

  74. DeVito, L. M. et al. Vasopressin 1b receptor knockout impairs memory for temporal order. J. Neurosci. 29, 2676–2683 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  76. Eichenbaum, H. & Cohen, N. J. Can we reconcile the declarative memory and spatial navigation views on hippocampal function? Neuron 83, 764–770 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Shimamura, A. P. Memory for the temporal order of events in patients with frontal lobe lesions and amnesic patients. Neuropsychologia 28, 803–813 (1990).

    CAS  PubMed  Google Scholar 

  78. Mayes, A. R. et al. Memory for single items, word pairs, and temporal order of different kinds in a patient with selective hippocampal lesions. Cogn. Neuropsychol. 18, 97–123 (2001).

    CAS  PubMed  Google Scholar 

  79. Spiers, H. J., Burgess, N., Hartley, T., Vargha-Khadem, F. & O'Keefe, J. Bilateral hippocampal pathology impairs topographical and episodic memory but not visual pattern matching. Hippocampus 11, 715–725 (2001).

    CAS  PubMed  Google Scholar 

  80. McDonough, L., Mandler, J. M., McKee, R. D. & Squire, L. R. The deferred imitation task as a nonverbal measure of declarative memory. Proc. Natl Acad. Sci. USA 92, 7580–7584 (1995).

    CAS  PubMed  Google Scholar 

  81. Adlam, A.-L., Vargha-Khadem, F., Mishkin, M. & de Haan, M. Deferrred imitation of action sequences in developmental amnesia. J. Cogn, Neurosci. 17, 240–248 (2005).

    Google Scholar 

  82. Konkel, A., Warren, D. E., Duff, M. C., Tranel, D. N. & Cohen, N. J. Hippocampal amnesia impaires all manner of relational memory. Front. Hum. Neurosci. 2, 15 (2008).

    PubMed  PubMed Central  Google Scholar 

  83. Fortin, N. J., Agster, K. L. & Eichenbaum, H. Critical role of the hippocampus in memory for sequences of events. Nature Neurosci. 5, 458–462 (2002). This study revealed that the hippocampus in rats is essential for remembering the order of a unique sequence of objects, even though it is not required to remember the objects themselves.

    CAS  PubMed  Google Scholar 

  84. Kesner, R. P. Gilbert, P. E. & Barua, L. A. The role of the hippocampus in memory for the temporal order of a sequence of odors. Behav. Neurosci. 116, 286–290 (2002).

    PubMed  Google Scholar 

  85. Agster, K. L., Fortin, N. J. & Eichenbaum, H. The hippocampus and disambiguation of overlapping sequences. J. Neurosci. 22, 5760–5768 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Devito, L. M. & Eichenbaum, H. Memory for the order of events in specific sequences: contributions of the hippocampus and medial prefrontal cortex. J. Neurosci. 31, 3169–3175 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  87. Ergorul, C. & Eichenbaum, H. The hippocampus and memory for “what,” “where,” and “when”. Learn. Mem. 11, 397–405 (2004).

    PubMed  PubMed Central  Google Scholar 

  88. Farovik, A., Dupont, L. M. & Eichenbaum, H. Distinct roles for dorsal CA3 and CA1 in memory for nonspatial sequential events. Learn. Mem. 17, 801–806 (2010).

    Google Scholar 

  89. Ergorul, C. & Eichenbaum, H. Essential role of the hippocampal formation in rapid learning of higher-order sequential associations. J. Neurosci. 26, 4111–4117 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. DeCoteau, W. E. & Kesner, R. P. A double dissociation between the rat hippocampus and medial caudoputamen in processing two forms of knowledge. Behav. Neurosci. 114, 1096–1108 (2000).

    CAS  PubMed  Google Scholar 

  91. Fouqet, C. et al. Complementary roles of the hippocampus and the dorsomedial striatum during spatial and sequence-based navigation behavior. PLoS ONE 8, e67232 (2013).

    Google Scholar 

  92. Kumaran, D. & Maguire, E. A. The dynamics of hippocampal activation during encoding of overlapping sequences. Neuron 49, 617–629 (2006).

    CAS  PubMed  Google Scholar 

  93. Ekstrom, A. D. & Bookheimer, S. Y. Spatial and temporal episodic memory retrieval recruit dissociable functional networks in the human brain. Learn. Mem. 14, 645–654 (2007).

    PubMed  PubMed Central  Google Scholar 

  94. Lehn, H. et al. A specific role of the human hippocampus in recall of temporal sequences. J. Neurosci. 29, 3475–3484 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Ross, R. S., Brown, T. I. & Stern, C. E. The retrieval of learned sequences engages the hippocampus: evidence from fMRI. Hippocampus 19, 790–799 (2009).

    PubMed  PubMed Central  Google Scholar 

  96. Kumaran, D. & Maguire, E. A. An unexpected sequence of events: mismatch detection in the human hippocampus. PLoS Biol. 4, e424 (2006).

    PubMed  PubMed Central  Google Scholar 

  97. Tubridy, S. & Davachi, L. Medial temporal lobe contributions to episodic sequence encoding. Cereb. Cortex 21, 272–280 (2011).

    PubMed  Google Scholar 

  98. Staresina, B. P. & Davachi, L. Differential encoding mechanisms for subsequent associative recognition and free recall. J. Neurosci. 26, 9162–9172 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Schendan, H. E., Searl, M. M., Melrose, R. J. & Stern, C. E. An fMRI study of the role of the medial temporal lobe in implicit and explicit sequence learning. Neuron 37, 1013–1025 (2003).

    CAS  PubMed  Google Scholar 

  100. Brown, T. I., Ross, R. S., Keller, J. B., Hasselmo, M. E. & Stern, C. E. Which way was I going? Contextual retrieval supports the disambiguation of well-learned overlapping navigational routes. J. Neurosci. 30, 7414–7422 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Jenkins, L. J. & Ranganath, C. Prefrontal and medial temporal lobe activity at encoding predicts temporal context memory. J. Neurosci. 30, 15558–15565 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  102. Schapiro, A. C., Kustner, L. V. & Turke-Browne, N. B. Shaping of object representations in the human medial temporal lobe based on temporal regularities. Curr. Biol. 22, 1622–1627 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  103. Copara, M. S. et al. Complementary roles of human hippocampal subregions during retrieval of spatiotemporal context. J. Neurosci. 34, 6834–6842 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. Ezzyat, Y. & Davachi, L. Similarity breeds proximity: pattern similarity within and across contexts is related to later mnemonic judgments of temporal proximity. Neuron 81, 1179–1189 (2014). This study uses multivoxel pattern analysis of functional MRI scans in humans to show that the similarity of representations across a series of events predicts the likelihood of remembering the order of those events, similar to findings in rodents based on neural ensemble firing patterns in reference 12.

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The author would like to acknowledge funding support from the US National Institutes of Mental Health (grants MH095297 and MH094263).

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Supplementary information S1 (movie)

Time cells in rats running on the treadmill. The firing patterns of three CA1 neurons are shown. For each, the time and location of the rat when individual spikes occur are plotted as dots (in a different colour for each neuron) on the rat's head. Note that even though the rat's head is approximately in the same location during the run, the neurons fire in sequence (pink then green then blue). Also note that each neuron additionally fires at a location on the maze outside the treadmill. The treadmill is on when a red triangle appears in bottom left corner. (MP4 5332 kb)

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Eichenbaum, H. Time cells in the hippocampus: a new dimension for mapping memories. Nat Rev Neurosci 15, 732–744 (2014). https://doi.org/10.1038/nrn3827

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