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.

  • Perspective
  • Published:

The grid code for ordered experience

Nature Reviews Neuroscience volume 22, pages 637–649 (2021)Cite this article

Subjects

Abstract

Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid pattern as well as responses of grid cells in contexts other than spatial navigation have presented a challenge to existing models of entorhinal function. In this Perspective, we propose that hippocampal input provides a key informative drive to the grid network in both spatial and non-spatial circumstances, particularly around salient events. We build on previous models in which neural activity propagates through the entorhinal–hippocampal network in time. This temporal contiguity in network activity points to temporal order as a necessary characteristic of representations generated by the hippocampal formation. We advocate that interactions in the entorhinal–hippocampal loop build a topological representation that is rooted in the temporal order of experience. In this way, the structure of grid cell firing supports a learned topology rather than a rigid coordinate frame that is bound to measurements of the physical world.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Fig. 1: Representations that are hypothesized to be supported by grid cells.
Fig. 2: Topological representations in the spike order of theta sequences.

Similar content being viewed by others

References

  1. Rowland, D. C., Roudi, Y., Moser, M. B. & Moser, E. I. Ten years of grid cells. Annu. Rev. Neurosci. 39, 19–40 (2016).

    Article  PubMed  CAS  Google Scholar 

  2. Hafting, T., Fyhn, M., Molden, S., Moser, M. B. & Moser, E. I. Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005).

    Article  PubMed  CAS  Google Scholar 

  3. Fyhn, M., Molden, S., Witter, M. P., Moser, E. I. & Moser, M. B. Spatial representation in the entorhinal cortex. Science 305, 1258–1264 (2004).

    Article  PubMed  CAS  Google Scholar 

  4. 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).

    Article  PubMed  Google Scholar 

  5. O’Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Clarendon Press, 1978).

  6. Tolman, E. C. Cognitive maps in rats and men. Psychol. Rev. 55, 189–208 (1948).

    Article  PubMed  CAS  Google Scholar 

  7. 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).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  9. Poucet, B. Spatial cognitive maps in animals: new hypotheses on their structure and neural mechanisms. Psychol. Rev. 100, 163–182 (1993).

    Article  PubMed  CAS  Google Scholar 

  10. Dabaghian, Y., Brandt, V. L. & Frank, L. M. Reconceiving the hippocampal map as a topological template. eLife 3, e03476 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  11. Buzsáki, G. & Tingley, D. Space and time: the hippocampus as a sequence generator. Trends Cogn. Sci. 22, 853–869 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Warren, W. H. Non-Euclidean navigation. J. Exp. Biol. 222 (Suppl. 1), jeb187971 (2019).

    Article  PubMed  Google Scholar 

  13. Muller, R. U., Stead, M. & Pach, J. The hippocampus as a cognitive graph. J. Gen. Physiol. 107, 663–694 (1996).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Dabaghian, Y. Through synapses to spatial memory maps via a topological model. Sci. Rep. 9, 572 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Bellmund, J. L. S., Gardenfors, P., Moser, E. I. & Doeller, C. F. Navigating cognition: spatial codes for human thinking. Science 362, eaat6766 (2018).

    Article  PubMed  CAS  Google Scholar 

  16. Park, S. A., Miller, D. S., Nili, H., Ranganath, C. & Boorman, E. D. Map making: constructing, combining, and inferring on abstract cognitive maps. Neuron https://doi.org/10.1016/j.neuron.2020.06.030 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Morton, N. W. & Preston, A. R. Concept formation as a computational cognitive process. Curr. Opin. Behav. Sci. 38, 83–89 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Fuhs, M. C. & Touretzky, D. S. A spin glass model of path integration in rat medial entorhinal cortex. J. Neurosci. 26, 4266–4276 (2006).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Burak, Y. & Fiete, I. R. Accurate path integration in continuous attractor network models of grid cells. PLoS Comput. Biol. 5, e1000291 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Guanella, A., Kiper, D. & Verschure, P. A model of grid cells based on a twisted torus topology. Int. J. Neural Syst. 17, 231–240 (2007).

    Article  PubMed  Google Scholar 

  21. McNaughton, B. L., Battaglia, F. P., Jensen, O., Moser, E. I. & Moser, M. B. Path integration and the neural basis of the ‘cognitive map’. Nat. Rev. Neurosci. 7, 663–678 (2006).

    Article  PubMed  CAS  Google Scholar 

  22. Couey, J. J. et al. Recurrent inhibitory circuitry as a mechanism for grid formation. Nat. Neurosci. 16, 318–324 (2013).

    Article  PubMed  CAS  Google Scholar 

  23. Pastoll, H., Solanka, L., van Rossum, M. C. & Nolan, M. F. Feedback inhibition enables θ-nested γ oscillations and grid firing fields. Neuron 77, 141–154 (2013).

    Article  PubMed  CAS  Google Scholar 

  24. Heys, J. G., Rangarajan, K. V. & Dombeck, D. A. The functional micro-organization of grid cells revealed by cellular-resolution imaging. Neuron 84, 1079–1090 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Yoon, K. et al. Specific evidence of low-dimensional continuous attractor dynamics in grid cells. Nat. Neurosci. 16, 1077–1084 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Zutshi, I. et al. Recurrent circuits within medial entorhinal cortex superficial layer support grid cell firing. Nat. Commun. 9, 3701 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Sargolini, F. et al. Conjunctive representation of position, direction, and velocity in entorhinal cortex. Science 312, 758–762 (2006).

    Article  PubMed  CAS  Google Scholar 

  28. McNaughton, B. L. et al. Deciphering the hippocampal polyglot: the hippocampus as a path integration system. J. Exp. Biol. 199, 173–185 (1996).

    Article  PubMed  CAS  Google Scholar 

  29. Moser, E. I., Moser, M. B. & McNaughton, B. L. Spatial representation in the hippocampal formation: a history. Nat. Neurosci. 20, 1448–1464 (2017).

    Article  PubMed  CAS  Google Scholar 

  30. Taube, J. S. The head direction signal: origins and sensory-motor integration. Annu. Rev. Neurosci. 30, 181–207 (2007).

    Article  PubMed  CAS  Google Scholar 

  31. Winter, S. S., Clark, B. J. & Taube, J. S. Disruption of the head direction cell network impairs the parahippocampal grid cell signal. Science 347, 870 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Munn, R. G. & Giocomo, L. M. Multiple head direction signals within entorhinal cortex: origin and function. Curr. Opin. Neurobiol. 64, 32–40 (2020).

    Article  PubMed  CAS  Google Scholar 

  33. Butler, W. N., Hardcastle, K. & Giocomo, L. M. Remembered reward locations restructure entorhinal spatial maps. Science 363, 1447–1452 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Fyhn, M., Hafting, T., Treves, A., Moser, M. B. & Moser, E. I. Hippocampal remapping and grid realignment in entorhinal cortex. Nature 446, 190–194 (2007).

    Article  PubMed  CAS  Google Scholar 

  35. Diehl, G. W., Hon, O. J., Leutgeb, S. & Leutgeb, J. K. Grid and nongrid cells in medial entorhinal cortex represent spatial location and environmental features with complementary coding schemes. Neuron 94, 83–92 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  36. Kropff, E., Carmichael, J. E., Moser, M. B. & Moser, E. I. Speed cells in the medial entorhinal cortex. Nature 523, 419–424 (2015).

    Article  PubMed  CAS  Google Scholar 

  37. Munn, R. G., Mallory, C. S., Hardcastle, K., Chetkovich, D. M. & Giocomo, L. M. Entorhinal velocity signals reflect environmental geometry. Nat. Neurosci. 23, 239–251 (2019).

    Article  CAS  Google Scholar 

  38. Carvalho, M. M. et al. A brainstem locomotor circuit drives the activity of speed cells in the medial entorhinal cortex. Cell Rep. 32, 108123 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Shipston-Sharman, O., Solanka, L. & Nolan, M. F. Continuous attractor network models of grid cell firing based on excitatory—inhibitory interactions. J. Physiol. 594, 6547–6557 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Hinman, J. R., Penley, S. C., Long, L. L., Escabí, M. A. & Chrobak, J. J. Septotemporal variation in dynamics of theta: speed and habituation. J. Neurophysiol. 105, 2675–2686 (2011).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Brandon, M. P. et al. Reduction of theta rhythm dissociates grid cell spatial periodicity from directional tuning. Science 332, 595–599 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Koenig, J., Linder, A. N., Leutgeb, J. K. & Leutgeb, S. The spatial periodicity of grid cells is not sustained during reduced theta oscillations. Science 332, 595–595 (2011).

    Article  CAS  Google Scholar 

  44. Ocko, S. A., Hardcastle, K., Giocomo, L. M. & Ganguli, S. Emergent elasticity in the neural code for space. Proc. Natl Acad. Sci. USA 115, E11798–E11806 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Hardcastle, K., Ganguli, S. & Giocomo, L. M. Environmental boundaries as an error correction mechanism for grid cells. Neuron 86, 827–839 (2015).

    Article  PubMed  CAS  Google Scholar 

  46. Bicanski, A. & Burgess, N. Neuronal vector coding in spatial cognition. Nat. Rev. Neurosci. 21, 453–470 (2020).

    Article  PubMed  CAS  Google Scholar 

  47. Stensola, H. et al. The entorhinal map is discretized. Nature 492, 72–78 (2012).

    Article  PubMed  CAS  Google Scholar 

  48. Fiete, I. R., Burak, Y. & Brookings, T. What grid cells convey about rat location. J. Neurosci. 28, 6858–6871 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Mathis, A., Herz, A. V. & Stemmler, M. Optimal population codes for space: grid cells outperform place cells. Neural Comput. 24, 2280–2317 (2012).

    Article  PubMed  Google Scholar 

  50. Widloski, J. & Fiete, I. R. A model of grid cell development through spatial exploration and spike time-dependent plasticity. Neuron 83, 481–495 (2014).

    Article  PubMed  CAS  Google Scholar 

  51. Sorscher, B., Mel, G. C., Ocko, S. A., Giocomo, L. & Ganguli, S. A unified theory for the computational and mechanistic origins of grid cells. Preprint at bioRxiv https://doi.org/10.1101/2020.12.29.424583 (2020).

    Article  Google Scholar 

  52. Burak, Y. Spatial coding and attractor dynamics of grid cells in the entorhinal cortex. Curr. Opin. Neurobiol. 25, 169–175 (2014).

    Article  PubMed  CAS  Google Scholar 

  53. Stemmler, M., Mathis, A. & Herz, A. V. Connecting multiple spatial scales to decode the population activity of grid cells. Sci. Adv. 1, e1500816 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Bush, D., Barry, C., Manson, D. & Burgess, N. Using grid cells for navigation. Neuron 87, 507–520 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Domnisoru, C., Kinkhabwala, A. A. & Tank, D. W. Membrane potential dynamics of grid cells. Nature 495, 199–204 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Schmidt-Hieber, C. & Häusser, M. Cellular mechanisms of spatial navigation in the medial entorhinal cortex. Nat. Neurosci. 16, 325–331 (2013).

    Article  PubMed  CAS  Google Scholar 

  57. Gu, Y. et al. A map-like micro-organization of grid cells in the medial entorhinal cortex. Cell 175, 736–750.e30 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Yoon, K., Lewallen, S., Kinkhabwala, A. A., Tank, D. W. & Fiete, I. R. Grid cell responses in 1D environments assessed as slices through a 2D lattice. Neuron 89, 1086–1099 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Trettel, S. G., Trimper, J. B., Hwaun, E., Fiete, I. R. & Colgin, L. L. Grid cell co-activity patterns during sleep reflect spatial overlap of grid fields during active behaviors. Nat. Neurosci. 22, 609–617 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Gardner, R. J., Lu, L., Wernle, T., Moser, M.-B. & Moser, E. I. Correlation structure of grid cells is preserved during sleep. Nat. Neurosci. 22, 598–608 (2019).

    Article  PubMed  CAS  Google Scholar 

  61. 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).

    Article  PubMed  CAS  Google Scholar 

  62. Miao, C., Cao, Q., Moser, M. B. & Moser, E. I. Parvalbumin and somatostatin interneurons control different space-coding networks in the medial entorhinal cortex. Cell 171, 507–521 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Barry, C., Hayman, R., Burgess, N. & Jeffery, K. J. Experience-dependent rescaling of entorhinal grids. Nat. Neurosci. 10, 682–684 (2007).

    Article  PubMed  CAS  Google Scholar 

  64. Krupic, J., Bauza, M., Burton, S., Barry, C. & O’Keefe, J. Grid cell symmetry is shaped by environmental geometry. Nature 518, 232–235 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Krupic, J., Bauza, M., Burton, S. & O’Keefe, J. Local transformations of the hippocampal cognitive map. Science 359, 1143–1146 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Keinath, A. T., Epstein, R. A. & Balasubramanian, V. Environmental deformations dynamically shift the grid cell spatial metric. eLife 7, e38169 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Barry, C., Ginzberg, L. L., O’Keefe, J. & Burgess, N. Grid cell firing patterns signal environmental novelty by expansion. Proc. Natl Acad. Sci. USA 43, 17687–17692 (2012).

    Article  Google Scholar 

  68. Wernle, T. et al. Integration of grid maps in merged environments. Nat. Neurosci. 21, 92–101 (2018).

    Article  PubMed  CAS  Google Scholar 

  69. Carpenter, F., Manson, D., Jeffery, K., Burgess, N. & Barry, C. Grid cells form a global representation of connected environments. Curr. Biol. 25, 1176–1182 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Boccara, C. N., Nardin, M., Stella, F., O’Neill, J. & Csicsvari, J. The entorhinal cognitive map is attracted to goals. Science 363, 1443–1447 (2019).

    Article  PubMed  CAS  Google Scholar 

  71. Ekstrom, A. D. & Ranganath, C. Space, time, and episodic memory: the hippocampus is all over the cognitive map. Hippocampus 28, 680–687 (2018).

    Article  PubMed  Google Scholar 

  72. Park, E. H., Keeley, S., Savin, C., Ranck, J. B. Jr & Fenton, A. A. How the internally organized direction sense is used to navigate. Neuron 101, 285–293.e5 (2019).

    Article  PubMed  CAS  Google Scholar 

  73. Hardcastle, K., Maheswaranathan, N., Ganguli, S. & Giocomo, L. M. A multiplexed, heterogeneous, and adaptive code for navigation in medial entorhinal cortex. Neuron 94, 375–387 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  74. Campbell, M. G. et al. Principles governing the integration of landmark and self-motion cues in entorhinal cortical codes for navigation. Nat. Neurosci. 21, 1096–1106 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Derdikman, D. et al. Fragmentation of grid cell maps in a multicompartment environment. Nat. Neurosci. 12, 1325–1332 (2009).

    Article  PubMed  CAS  Google Scholar 

  76. Pröll, M., Häusler, S. & Herz, A. V. M. Grid-cell activity on linear tracks indicates purely translational remapping of 2D firing patterns at movement turning points. J. Neurosci. 38, 7004–7011 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  77. Mizuseki, K., Sirota, A., Pastalkova, E. & Buzsáki, G. Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop. Neuron 64, 267–280 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Whitlock, J. R. & Derdikman, D. Head direction maps remain stable despite grid map fragmentation. Front. Neural Circuits 6, 9 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  79. Raudies, F., Brandon, M. P., Chapman, G. W. & Hasselmo, M. E. Head direction is coded more strongly than movement direction in a population of entorhinal neurons. Brain Res. 1621, 355–367 (2015).

    Article  PubMed  CAS  Google Scholar 

  80. Gerlei, K. et al. Grid cells are modulated by local head direction. Nat. Commun. 11, 4228 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  81. Ismakov, R., Barak, O., Jeffery, K. & Derdikman, D. Grid cells encode local positional information. Curr. Biol. 27, 2337–2343 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  82. Dunn, B., Wennberg, D., Huang, Z. & Roudi, Y. Grid cells show field-to-field variability and this explains the aperiodic response of inhibitory interneurons. Preprint at https://arxiv.org/abs/1701.04893 (2017).

  83. Kanter, B. R. et al. A novel mechanism for the grid-to-place cell transformation revealed by transgenic depolarization of medial entorhinal cortex layer II. Neuron 93, 1480–1492 (2017).

    Article  PubMed  CAS  Google Scholar 

  84. Nagele, J., Herz, A. V. M. & Stemmler, M. B. Untethered firing fields and intermittent silences: why grid-cell discharge is so variable. Hippocampus 30, 367–383 (2020).

    Article  PubMed  Google Scholar 

  85. Meister, M. L. R. & Buffalo, E. A. Neurons in primate entorhinal cortex represent gaze position in multiple spatial reference frames. J. Neurosci. 38, 2430–2441 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  87. Kraus, B. J. et al. During running in place, grid cells integrate elapsed time and distance run. Neuron 88, 578–589 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  88. Heys, J. G. & Dombeck, D. A. Evidence for a subcircuit in medial entorhinal cortex representing elapsed time during immobility. Nat. Neurosci. 21, 1574–1582 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Jacobs, J. et al. Direct recordings of grid-like neuronal activity in human spatial navigation. Nat. Neurosci. 16, 1188–1190 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  90. Killian, N. J., Jutras, M. J. & Buffalo, E. A. A map of visual space in the primate entorhinal cortex. Nature 491, 761–764 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. Wilming, N., Konig, P., Konig, S. & Buffalo, E. A. Entorhinal cortex receptive fields are modulated by spatial attention, even without movement. eLife 7, e31745 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  92. Doeller, C. F., Barry, C. & Burgess, N. Evidence for grid cells in a human memory network. Nature 463, 657–661 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Epstein, R. A., Patai, E. Z., Julian, J. B. & Spiers, H. J. The cognitive map in humans: spatial navigation and beyond. Nat. Neurosci. 20, 1504–1513 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  94. Behrens, T. E. J. et al. What is a cognitive map? Organizing knowledge for flexible behavior. Neuron 100, 490–509 (2018).

    Article  PubMed  CAS  Google Scholar 

  95. Howard, L. R. et al. The hippocampus and entorhinal cortex encode the path and Euclidean distances to goals during navigation. Curr. Biol. 24, 1331–1340 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Constantinescu, A. O., O’Reilly, J. X. & Behrens, T. E. Organizing conceptual knowledge in humans with a gridlike code. Science 352, 1464–1468 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  97. Garvert, M. M., Dolan, R. J. & Behrens, T. E. J. A map of abstract relational knowledge in the human hippocampal–entorhinal cortex. eLife 6, e17086 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  98. Liu, Y., Dolan, R. J., Kurth-Nelson, Z. & Behrens, T. E. J. Human replay spontaneously reorganizes experience. Cell 178, 640–652.e14 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Theves, S., Fernandez, G. & Doeller, C. F. The hippocampus encodes distances in multidimensional feature space. Curr. Biol. 29, 1226–1231.e3 (2019).

    Article  PubMed  CAS  Google Scholar 

  100. Schapiro, A. C., Turk-Browne, N. B., Norman, K. A. & Botvinick, M. M. Statistical learning of temporal community structure in the hippocampus. Hippocampus 26, 3–8 (2016).

    Article  PubMed  Google Scholar 

  101. Herzog, L. E. et al. Interaction of taste and place coding in the hippocampus. J. Neurosci. 39, 3057–3069 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Gener, T., Perez-Mendez, L. & Sanchez-Vives, M. V. Tactile modulation of hippocampal place fields. Hippocampus 23, 1453–1462 (2013).

    Article  PubMed  Google Scholar 

  103. Wood, E. R., Dudchenko, P. A. & Eichenbaum, H. The global record of memory in hippocampal neuronal activity. Nature 397, 613–616 (1999).

    Article  PubMed  CAS  Google Scholar 

  104. Rutishauser, U., Reddy, L., Mormann, F. & Sarnthein, J. The architecture of human memory: insights from human single-neuron recordings. J. Neurosci. 41, 883–890 (2021).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. Rueckemann, J. W. & Buffalo, E. A. Spatial responses, immediate experience, and memory in the monkey hippocampus. Curr. Opin. Behav. Sci. 17, 155–160 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  106. Radvansky, B. A. & Dombeck, D. A. An olfactory virtual reality system for mice. Nat. Commun. 9, 839 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  108. Allen, T. A., Salz, D. M., McKenzie, S. & Fortin, N. J. Nonspatial sequence coding in CA1 neurons. J. Neurosci. 36, 1547–1563 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  109. Terada, S., Sakurai, Y., Nakahara, H. & Fujisawa, S. Temporal and rate coding for discrete event sequences in the hippocampus. Neuron 94, 1248–1262.e4 (2017).

    Article  PubMed  CAS  Google Scholar 

  110. Taxidis, J. et al. Differential emergence and stability of sensory and temporal representations in context-specific hippocampal sequences. Neuron 108, 984–998.e9 (2020).

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  111. Eichenbaum, H. Time cells in the hippocampus: a new dimension for mapping memories. Nat. Rev. Neurosci. 15, 732–744 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  112. Pastalkova, E., Itskov, V., Amarasingham, A. & Buzsaki, G. Internally generated cell assembly sequences in the rat hippocampus. Science 321, 1322–1327 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  113. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  114. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  115. Naya, Y. & Suzuki, W. A. Integrating what and when across the primate medial temporal lobe. Science 333, 773–776 (2011).

    Article  PubMed  CAS  Google Scholar 

  116. Sakon, J. J., Naya, Y., Wirth, S. & Suzuki, W. A. Context-dependent incremental timing cells in the primate hippocampus. Proc. Natl Acad. Sci. USA 111, 18351–18356 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  118. Sun, C., Yang, W., Martin, J. & Tonegawa, S. Hippocampal neurons represent events as transferable units of experience. Nat. Neurosci. 23, 651–663 (2020).

    Article  PubMed  CAS  Google Scholar 

  119. Klukas, M., Lewis, M. & Fiete, I. Efficient and flexible representation of higher-dimensional cognitive variables with grid cells. PLoS Comput. Biol. 16, e1007796 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Buffalo, E. A. Bridging the gap between spatial and mnemonic views of the hippocampal formation. Hippocampus 25, 713–718 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Kornienko, O., Latuske, P., Bassler, M., Kohler, L. & Allen, K. Non-rhythmic head-direction cells in the parahippocampal region are not constrained by attractor network dynamics. eLife 7, e35949 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  122. Muessig, L., Hauser, J., Wills, T. J. & Cacucci, F. A developmental switch in place cell accuracy coincides with grid cell maturation. Neuron 86, 1167–1173 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Langston, R. F. et al. Development of the spatial representation system in the rat. Science 328, 1576–1580 (2010).

    Article  PubMed  CAS  Google Scholar 

  124. Wills, T. J., Cacucci, F., Burgess, N. & O’Keefe, J. Development of the hippocampal cognitive map in preweanling rats. Science 328, 1573–1576 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  125. Tan, H. M., Wills, T. J. & Cacucci, F. The development of spatial and memory circuits in the rat. Wiley Interdiscip. Rev. Cogn. Sci https://doi.org/10.1002/wcs.1424 (2017).

    Article  PubMed  Google Scholar 

  126. Bonnevie, T. et al. Grid cells require excitatory drive from the hippocampus. Nat. Neurosci. 16, 309–317 (2013).

    Article  PubMed  CAS  Google Scholar 

  127. Almog, N. et al. During hippocampal inactivation, grid cells maintain synchrony, even when the grid pattern is lost. eLife 8, e47147 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  128. Agmon, H. & Burak, Y. A theory of joint attractor dynamics in the hippocampus and the entorhinal cortex accounts for artificial remapping and grid cell field-to-field variability. eLife 9, e56894 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  129. Castro, L. & Aguiar, P. A feedforward model for the formation of a grid field where spatial information is provided solely from place cells. Biol. Cybern. 108, 133–143 (2014).

    Article  PubMed  Google Scholar 

  130. Kropff, E. & Treves, A. The emergence of grid cells: intelligent design or just adaptation? Hippocampus 18, 1256–1269 (2008).

    Article  PubMed  Google Scholar 

  131. Weber, S. N. & Sprekeler, H. Learning place cells, grid cells and invariances with excitatory and inhibitory plasticity. eLife 7, e34560 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Si, B. & Treves, A. A model for the differentiation between grid and conjunctive units in medial entorhinal cortex. Hippocampus 23, 1410–1424 (2013).

    Article  PubMed  Google Scholar 

  133. Samu, D., Eros, P., Ujfalussy, B. & Kiss, T. Robust path integration in the entorhinal grid cell system with hippocampal feed-back. Biol. Cybern. 101, 19–34 (2009).

    Article  PubMed  Google Scholar 

  134. Renno-Costa, C. & Tort, A. B. L. Place and grid cells in a loop: implications for memory function and spatial coding. J. Neurosci. 37, 8062–8076 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  135. de Cothi, W. & Barry, C. Neurobiological successor features for spatial navigation. Hippocampus 30, 1347–1355 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Stachenfeld, K. L., Botvinick, M. M. & Gershman, S. J. The hippocampus as a predictive map. Nat. Neurosci. 20, 1643–1653 (2017).

    Article  PubMed  CAS  Google Scholar 

  137. Dordek, Y., Soudry, D., Meir, R. & Derdikman, D. Extracting grid cell characteristics from place cell inputs using non-negative principal component analysis. eLife 5, e10094 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Kurikawa, T., Mizuseki, K. & Fukai, T. Oscillation-driven memory encoding, maintenance, and recall in an entorhinal-hippocampal circuit model. Cereb. Cortex 31, 2038–2057 (2020).

    Article  Google Scholar 

  139. Buzsáki, G. Theta oscillations in the hippocampus. Neuron 33, 325–340 (2002).

    Article  PubMed  Google Scholar 

  140. Tamamaki, N. & Nojyo, Y. Preservation of topography in the connections between the subiculum, field CA1, and the entorhinal cortex in rats. J. Comp. Neurol. 353, 379–390 (1995).

    Article  PubMed  CAS  Google Scholar 

  141. Cenquizca, L. A. & Swanson, L. W. Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex. Brain Res. Rev. 56, 1–26 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Kloosterman, F., Van Haeften, T., Witter, M. P. & Lopes da Silva, F. H. Electrophysiological characterization of interlaminar entorhinal connections: an essential link for re-entrance in the hippocampal — entorhinal system. Eur. J. Neurosci. 18, 3037–3052 (2003).

    Article  PubMed  Google Scholar 

  143. Beed, P. et al. Analysis of excitatory microcircuitry in the medial entorhinal cortex reveals cell-type-specific differences. Neuron 68, 1059–1066 (2010).

    Article  PubMed  CAS  Google Scholar 

  144. Lovett-Barron, M. & Losonczy, A. Circuits supporting the grid. Nat. Neurosci. 16, 255–257 (2013).

    Article  PubMed  CAS  Google Scholar 

  145. Villette, V., Malvache, A., Tressard, T., Dupuy, N. & Cossart, R. Internally recurring hippocampal sequences as a population template of spatiotemporal information. Neuron 88, 357–366 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  146. Robinson, N. T. M. et al. Medial entorhinal cortex selectively supports temporal coding by hippocampal neurons. Neuron 94, 677–688.e6 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  147. Ekstrom, A. D., Harootonian, S. K. & Huffman, D. J. Grid coding, spatial representation, and navigation: should we assume an isomorphism? Hippocampus 30, 422–432 (2020).

    Article  PubMed  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  149. Foster, D. J. & Wilson, M. A. Hippocampal theta sequences. Hippocampus 17, 1093–1099 (2007).

    Article  PubMed  Google Scholar 

  150. Skaggs, W. E., McNaughton, B. L., Wilson, M. A. & Barnes, C. A. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

    Article  PubMed  CAS  Google Scholar 

  151. Buzsáki, G. Neural syntax: cell assemblies, synapsembles, and readers. Neuron 68, 362–385 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  152. Zutshi, I., Leutgeb, J. K. & Leutgeb, S. Theta sequences of grid cell populations can provide a movement-direction signal. Curr. Opn. Behav. Sci. 17, 147–154 (2017).

    Article  Google Scholar 

  153. Kang, L. & DeWeese, M. R. Replay as wavefronts and theta sequences as bump oscillations in a grid cell attractor network. eLife 8, e46351 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  154. Hafting, T., Fyhn, M., Bonnevie, T., Moser, M.-B. & Moser, E. I. Hippocampus-independent phase precession in entorhinal grid cells. Nature 453, 1248–1252 (2008).

    Article  PubMed  CAS  Google Scholar 

  155. Schlesiger, M. I. et al. The medial entorhinal cortex is necessary for temporal organization of hippocampal neuronal activity. Nat. Neurosci. 18, 1123–1132 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  156. Feng, T., Silva, D. & Foster, D. J. Dissociation between the experience-dependent development of hippocampal theta sequences and single-trial phase precession. J. Neurosci. 35, 4890–4902 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  157. Wang, Y., Romani, S., Lustig, B., Leonardo, A. & Pastalkova, E. Theta sequences are essential for internally generated hippocampal firing fields. Nat. Neurosci. 18, 282–288 (2015).

    Article  PubMed  CAS  Google Scholar 

  158. Robbe, D. & Buzsaki, G. Alteration of theta timescale dynamics of hippocampal place cells by a cannabinoid is associated with memory impairment. J. Neurosci. 29, 12597–12605 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  159. Bolding, K. A., Ferbinteanu, J., Fox, S. E. & Muller, R. U. Place cell firing cannot support navigation without intact septal circuits. Hippocampus 30, 175–191 (2020).

    Article  PubMed  Google Scholar 

  160. Siegle, J. H. & Wilson, M. A. Enhancement of encoding and retrieval functions through theta phase-specific manipulation of hippocampus. eLife 3, e03061 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Yartsev, M. M., Witter, M. P. & Ulanovsky, N. Grid cells without theta oscillations in the entorhinal cortex of bats. Nature 479, 103–107 (2011).

    Article  PubMed  CAS  Google Scholar 

  162. Qasim, S. E., Fried, I. & Jacobs, J. Phase precession in the human hippocampus and entorhinal cortex. Preprint at bioRxiv https://doi.org/10.1101/2020.09.06.285320 (2020).

    Article  Google Scholar 

  163. Killian, N. J., Jutras, M. J. & Buffalo, E. A. A map of visual space in the primate entorhinal cortex. Nature 491, 761–764 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  164. Hollup, S. A., Molden, S., Donnett, J. G., Moser, M. B. & Moser, E. I. Accumulation of hippocampal place fields at the goal location in an annular watermaze task. J. Neurosci. 21, 1635–1644 (2001).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  166. Momennejad, I. Learning structures: predictive representations, replay, and generalization. Curr. Opin. Behav. Sci. 32, 155–166 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  168. Lipton, P. A., White, J. A. & Eichenbaum, H. Disambiguation of overlapping experiences by neurons in the medial entorhinal cortex. J. Neurosci. 27, 5787–5795 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  169. Wood, E. R., Dudchenko, P. A., 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).

    Article  PubMed  CAS  Google Scholar 

  170. Grieves, R. M., Wood, E. R. & Dudchenko, P. A. Place cells on a maze encode routes rather than destinations. eLife 5, e15986 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  171. Ferbinteanu, J. & Shapiro, M. L. Prospective and retrospective memory coding in the hippocampus. Neuron 40, 1227–1239 (2003).

    Article  PubMed  CAS  Google Scholar 

  172. McNamee, D. C., Stachenfeld, K. L., Botvinick, M. M. & Gershman, S. J. Flexible modulation of sequence generation in the entorhinal–hippocampal system. Nat. Neurosci. https://doi.org/10.1038/s41593-021-00831-7 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  173. Hales, J. B. et al. Medial entorhinal cortex lesions only partially disrupt hippocampal place cells and hippocampus-dependent place memory. Cell Rep. 9, 893–901 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  174. Miller, V. M. & Best, P. J. Spatial correlates of hippocampal unit activity are altered by lesions of the fornix and entorhinal cortex. Brain Res. 194, 311–323 (1980).

    Article  PubMed  CAS  Google Scholar 

  175. Schlesiger, M. I., Boublil, B. L., Hales, J. B., Leutgeb, J. K. & Leutgeb, S. Hippocampal global remapping can occur without input from the medial entorhinal cortex. Cell Rep. 22, 3152–3159 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  176. Van Cauter, T., Poucet, B. & Save, E. Unstable CA1 place cell representation in rats with entorhinal cortex lesions. Eur. J. Neurosci. 27, 1933–1946 (2008).

    Article  PubMed  Google Scholar 

  177. Miao, C. et al. Hippocampal remapping after partial inactivation of the medial entorhinal cortex. Neuron 88, 590–603 (2015).

    Article  PubMed  CAS  Google Scholar 

  178. Rueckemann, J. W. et al. Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons. Hippocampus 26, 246–260 (2016).

    Article  PubMed  Google Scholar 

  179. Navawongse, R. & Eichenbaum, H. Distinct pathways for rule-based retrieval and spatial mapping of memory representations in hippocampal neurons. J. Neurosci. 33, 1002–1013 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  180. Ormond, J. & McNaughton, B. L. Place field expansion after focal MEC inactivations is consistent with loss of Fourier components and path integrator gain reduction. Proc. Natl Acad. Sci. USA 112, 4116–4121 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  181. Zhao, R. et al. Impaired recall of positional memory following chemogenetic disruption of place field stability. Cell Rep. 16, 793–804 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  182. Mallory, C. S., Hardcastle, K., Bant, J. S. & Giocomo, L. M. Grid scale drives the scale and long-term stability of place maps. Nat. Neurosci. 21, 270–282 (2018).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Brandon, M. P., Koenig, J., Leutgeb, J. K. & Leutgeb, S. New and distinct hippocampal place codes are generated in a new environment during septal inactivation. Neuron 82, 789–796 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  185. Levy, W. B. A sequence predicting CA3 is a flexible associator that learns and uses context to solve hippocampal-like tasks. Hippocampus 6, 579–590 (1996).

    Article  PubMed  CAS  Google Scholar 

  186. Giocomo, L. M. Environmental boundaries as a mechanism for correcting and anchoring spatial maps. J. Physiol. 594, 6501–6511 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  187. Dombeck, D. A., Harvey, C. D., Tian, L., Looger, L. L. & Tank, D. W. Functional imaging of hippocampal place cells at cellular resolution during virtual navigation. Nat. Neurosci. 13, 1433–1440 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  189. McKenzie, S. & Buzsáki, G. Micro-, Meso- and Macro-Dynamics of the Brain (eds Buzsáki, G. & Christen, Y.) 1–21 (Springer, 2016).

  190. Munn, R. G. K., Mallory, C. S., Hardcastle, K., Chetkovich, D. M. & Giocomo, L. M. Entorhinal velocity signals reflect environmental geometry. Nat. Neurosci. 23, 239–251 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  191. Muller, R. U. & Kubie, J. L. The effects of changes in the environment on the spatial firing of hippocampal complex-spike cells. J. Neurosci. 7, 1951–1968 (1987).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  192. Gothard, K. M., Skaggs, W. E. & McNaughton, B. L. Dynamics of mismatch correction in the hippocampal ensemble code for space: interaction between path integration and environmental cues. J. Neurosci. 16, 8027–8040 (1996).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  193. Diba, K. & Buzsaki, G. Hippocampal network dynamics constrain the time lag between pyramidal cells across modified environments. J. Neurosci. 28, 13448–13456 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  194. Sheehan, D. J., Charczynski, S. & Fordyce, B. A. A compressed representation of spatial distance in the rodent hippocampus. Preprint at bioRxiv https://doi.org/10.1101/2021.02.15.431306 (2021).

    Article  Google Scholar 

  195. Shimbo, A., Izawa, E.-I. & Fujisawa, S. Scalable representation of time in the hippocampus. Sci. Adv. 7, eabd7013 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  196. Kubie, J. L., Levy, E. R. J. & Fenton, A. A. Is hippocampal remapping the physiological basis for context? Hippocampus 30, 851–864 (2020).

    Article  PubMed  Google Scholar 

  197. Warren, W. H., Rothman, D. B., Schnapp, B. H. & Ericson, J. D. Wormholes in virtual space: from cognitive maps to cognitive graphs. Cognition 166, 152–163 (2017).

    Article  PubMed  Google Scholar 

  198. Gupta, A. S., van der Meer, M. A. A., Touretzky, D. S. & David Redish, A. Segmentation of spatial experience by hippocampal theta sequences. Nat. Neurosci. 15, 1032–1039 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  200. 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).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  201. Kay, K. et al. Constant sub-second cycling between representations of possible futures in the hippocampus. Cell 180, 552–567 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  202. Gupta, A. S., van der Meer, M. A., Touretzky, D. S. & Redish, A. D. Segmentation of spatial experience by hippocampal theta sequences. Nat. Neurosci. 15, 1032–1039 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  203. Whittington, J. C. R. et al. The Tolman-Eichenbaum machine: unifying space and relational memory through generalization in the hippocampal formation. Cell 183, 1249–1263.e23 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  204. Momennejad, I. et al. The successor representation in human reinforcement learning. Nat. Hum. Behav. 1, 680–692 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  205. Dayan, P. Improving generalization for temporal difference learning: the successor representation. Neural Comput. 5, 613–624 (1993).

    Article  Google Scholar 

  206. Dabaghian, Y., Mémoli, F., Frank, L. & Carlsson, G. A topological paradigm for hippocampal spatial map formation using persistent homology. PLoS Comput. Biol. 8, e1002581 (2012).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  207. Chen, Z., Gomperts, S. N., Yamamoto, J. & Wilson, M. A. Neural representation of spatial topology in the rodent hippocampus. Neural Comput. 26, 1–39 (2014).

    Article  PubMed  Google Scholar 

  208. Curto, C. & Itskov, V. Cell groups reveal structure of stimulus space. PLoS Comput. Biol. 4, e1000205 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  210. Mok, R. M. & Love, B. C. A non-spatial account of place and grid cells based on clustering models of concept learning. Nat. Commun. 10, 5685 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  211. Savelli, F., Yoganarasimha, D. & Knierim, J. J. Influence of boundary removal on the spatial representations of the medial entorhinal cortex. Hippocampus 18, 1270–1282 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  212. Solstad, T., Boccara, C. N., Kropff, E., Moser, M. B. & Moser, E. I. Representation of geometric borders in the entorhinal cortex. Science 322, 1865–1868 (2008).

    Article  PubMed  CAS  Google Scholar 

  213. Taube, J. S., Muller, R. U. & Ranck, J. B. Jr Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis. J. Neurosci. 10, 420–435 (1990).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  214. Buetfering, C., Allen, K. & Monyer, H. Parvalbumin interneurons provide grid cell–driven recurrent inhibition in the medial entorhinal cortex. Nat. Neurosci. 17, 710–718 (2014).

    Article  PubMed  CAS  Google Scholar 

  215. Dhillon, A. & Jones, R. S. Laminar differences in recurrent excitatory transmission in the rat entorhinal cortex in vitro. Neuroscience 99, 413–422 (2000).

    Article  PubMed  CAS  Google Scholar 

  216. Fuchs, E. C. et al. Local and distant input controlling excitation in layer II of the medial entorhinal cortex. Neuron 89, 194–208 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  217. Winterer, J. et al. Excitatory microcircuits within superficial layers of the medial entorhinal cortex. Cell Rep. 19, 1110–1116 (2017).

    Article  PubMed  CAS  Google Scholar 

  218. Sun, C. et al. Distinct speed dependence of entorhinal island and ocean cells, including respective grid cells. Proc. Natl Acad. Sci. USA 112, 9466–9471 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  219. Tang, Q. et al. Pyramidal and stellate cell specificity of grid and border representations in layer 2 of medial entorhinal cortex. Neuron 84, 1191–1197 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  220. Alonso, A. & Klink, R. Differential electroresponsiveness of stellate and pyramidal-like cells of medial entorhinal cortex layer II. J. Neurophysiol. 70, 128–143 (1993).

    Article  PubMed  CAS  Google Scholar 

  221. Canto, C. B. & Witter, M. P. Cellular properties of principal neurons in the rat entorhinal cortex. II. The medial entorhinal cortex. Hippocampus 22, 1277–1299 (2012).

    Article  PubMed  Google Scholar 

  222. Ohara, S. et al. Intrinsic projections of layer Vb neurons to layers Va, III, and II in the lateral and medial entorhinal cortex of the rat. Cell Rep. 24, 107–116 (2018).

    Article  PubMed  CAS  Google Scholar 

  223. Surmeli, G. et al. Molecularly defined circuitry reveals input-output segregation in deep layers of the medial entorhinal cortex. Neuron 88, 1040–1053 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  224. Giocomo, L. M., Moser, M. B. & Moser, E. I. Computational models of grid cells. Neuron 71, 589–603 (2011).

    Article  PubMed  CAS  Google Scholar 

  225. Van Strien, N. M., Cappaert, N. L. M. & Witter, M. P. The anatomy of memory: an interactive overview of the parahippocampal — hippocampal network. Nat. Rev. Neurosci. 10, 272–282 (2009).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  227. Ray, S. et al. Grid-layout and theta-modulation of layer 2 pyramidal neurons in medial entorhinal cortex. Science 343, 891–896 (2014).

    Article  PubMed  CAS  Google Scholar 

  228. Deadwyler, S. A., West, J. R., Cotman, C. W. & Lynch, G. Physiological studies of the reciprocal connections between the hippocampus and entorhinal cortex. Exp. Neurol. 49, 35–57 (1975).

    Article  PubMed  CAS  Google Scholar 

  229. Witter, M. P., Wouterlood, F. G., Naber, P. A. & Van Haeften, T. Anatomical organization of the parahippocampal-hippocampal network. Ann. NY Acad. Sci. 911, 1–24 (2000).

    Article  PubMed  CAS  Google Scholar 

  230. Rowland, D. C. et al. Transgenically targeted rabies virus demonstrates a major monosynaptic projection from hippocampal area CA2 to medial entorhinal layer II neurons. J. Neurosci. 33, 14889–14898 (2013).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  231. Canto, C. B., Wouterlood, F. G. & Witter, M. P. What does the anatomical organization of the entorhinal cortex tell us? Neural Plast. 2008, 381243 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank A. Alexander, L. Rangel, T. Fisher, M. Klukas, W. Mau and E. Aery Jones for comments on the original manuscript and helpful discussion. The authors also thank the reviewers for their thoughtful and constructive criticism, which helped improve the manuscript. This work was supported by the Helen Hay Whitney Foundation for M.S., by the US Office of Naval Research (N00141812690), the Simons Foundation (542987SPI), the Vallee Foundation and the James S McDonnell Foundation for L.M.G and by the McKnight Foundation, the Simons Foundation, the NIH Office of the Director (P51 OD010425), the US National Institute of Neurological Disorders and Stroke (U19NS107609) and the US National Institute of Mental Health (MH080007 and MH117777) for E.A.B.

Author information

Author notes

  1. These authors contributed equally: J. W. Rueckemann and M. Sosa.

  2. These authors jointly supervised this work: E. A. Buffalo and L. M. Giocomo.

Authors and Affiliations

  1. Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA, USA

    Jon W. Rueckemann & Elizabeth A. Buffalo

  2. Washington National Primate Research Center, Seattle, WA, USA

    Jon W. Rueckemann & Elizabeth A. Buffalo

  3. Department of Neurobiology, Stanford University School of Medicine, Stanford, CA, USA

    Marielena Sosa & Lisa M. Giocomo

Authors
  1. Jon W. Rueckemann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Marielena Sosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lisa M. Giocomo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elizabeth A. Buffalo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed equally to the conceptualization and writing of the manuscript.

Corresponding authors

Correspondence to Lisa M. Giocomo or Elizabeth A. Buffalo.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Neuroscience thanks C. Ranganath; J. Whittington, who co-reviewed with T. Behrens; and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

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

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rueckemann, J.W., Sosa, M., Giocomo, L.M. et al. The grid code for ordered experience. Nat Rev Neurosci 22, 637–649 (2021). https://doi.org/10.1038/s41583-021-00499-9

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41583-021-00499-9

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