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Microstructure of a spatial map in the entorhinal cortex


The ability to find one's way depends on neural algorithms that integrate information about place, distance and direction, but the implementation of these operations in cortical microcircuits is poorly understood. Here we show that the dorsocaudal medial entorhinal cortex (dMEC) contains a directionally oriented, topographically organized neural map of the spatial environment. Its key unit is the ‘grid cell’, which is activated whenever the animal's position coincides with any vertex of a regular grid of equilateral triangles spanning the surface of the environment. Grids of neighbouring cells share a common orientation and spacing, but their vertex locations (their phases) differ. The spacing and size of individual fields increase from dorsal to ventral dMEC. The map is anchored to external landmarks, but persists in their absence, suggesting that grid cells may be part of a generalized, path-integration-based map of the spatial environment.

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Figure 1: Firing fields of grid cells have a repetitive triangular structure.
Figure 2: Grid cells recorded simultaneously at two electrode locations in the same rat.
Figure 3: Distributed spatial phase of co-localized grid cells.
Figure 4: Grids are aligned to environment-specific landmarks.
Figure 5: Grids persist in darkness.
Figure 6: Grid structure of dMEC cells is expressed instantly in a novel environment.

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  1. O'Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Clarendon, Oxford, 1978)

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  3. Taube, J. S. Head direction cells and the neurophysiological basis for a sense of direction. Prog. Neurobiol. 55, 225–256 (1998)

    Article  CAS  Google Scholar 

  4. Redish, A. D. & Touretzky, D. S. Cognitive maps beyond the hippocampus. Hippocampus 7, 15–35 (1997)

    Article  CAS  Google Scholar 

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

    Book  Google Scholar 

  6. Sharp, P. E. Complimentary roles for hippocampal versus subicular/entorhinal place cells in coding place, context, and events. Hippocampus 9, 432–443 (1999)

    Article  CAS  Google Scholar 

  7. Etienne, A. S. & Jeffery, K. J. Path integration in mammals. Hippocampus 14, 180–192 (2004)

    Article  Google Scholar 

  8. O'Keefe, J. & Conway, D. H. Hippocampal place units in the freely moving rat: why they fire where they fire. Exp. Brain Res. 31, 573–590 (1978)

    Article  CAS  Google Scholar 

  9. O'Keefe, J. & Burgess, N. Geometric determinants of the place fields of hippocampal neurons. Nature 381, 425–428 (1996)

    Article  ADS  CAS  Google Scholar 

  10. 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  CAS  Google Scholar 

  11. Sharp, P. E., Blair, H. T., Etkin, D. & Tzanetos, D. B. Influences of vestibular and visual motion information on the spatial firing patterns of hippocampal place cells. J. Neurosci. 15, 173–189 (1995)

    Article  CAS  Google Scholar 

  12. Knierim, J. J., Kudrimoti, H. S. & McNaughton, B. L. Place cells, head direction cells, and the learning of landmark stability. J. Neurosci. 15, 1648–1659 (1995)

    Article  CAS  Google Scholar 

  13. Jeffery, K. J., Donnett, J. G., Burgess, N. & O'Keefe, J. M. Directional control of hippocampal place fields. Exp. Brain Res. 117, 131–142 (1997)

    Article  CAS  Google Scholar 

  14. Nadel, L. The hippocampus and space revisited. Hippocampus 1, 221–229 (1991)

    Article  CAS  Google Scholar 

  15. Samsonovich, A. & McNaughton, B. L. Path integration and cognitive mapping in a continuous attractor neural network model. J. Neurosci. 17, 5900–5920 (1997)

    Article  CAS  Google Scholar 

  16. 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  CAS  Google Scholar 

  17. Bostock, E., Muller, R. U. & Kubie, J. L. Experience-dependent modifications of hippocampal place cell firing. Hippocampus 1, 193–205 (1991)

    Article  CAS  Google Scholar 

  18. Leutgeb, S., Leutgeb, J. K., Treves, A., Moser, M.-B. & Moser, E. I. Distinct ensemble codes in hippocampal areas CA3 and CA1. Science 305, 1295–1298 (2004)

    Article  ADS  CAS  Google Scholar 

  19. Markus, E. J. et al. Interactions between location and task affect the spatial and directional firing of hippocampal neurons. J. Neurosci. 15, 7079–7094 (1995)

    Article  MathSciNet  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  21. 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  CAS  Google Scholar 

  22. Nakazawa, K. et al. Requirement for hippocampal CA3 NMDA receptors in associative memory recall. Science 297, 211–218 (2002)

    Article  ADS  CAS  Google Scholar 

  23. Lee, I., Yoganarasimha, D., Rao, G. & Knierim, J. J. Comparison of population coherence of place cells in hippocampal subfields CA1 and CA3. Nature 430, 456–459 (2004)

    Article  ADS  CAS  Google Scholar 

  24. Rolls, E. T. & Treves, A. Neural Networks and Brain Function (Oxford Univ. Press, Oxford, 1998)

    Google Scholar 

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

    Article  CAS  Google Scholar 

  26. 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  ADS  CAS  Google Scholar 

  27. Wilson, M. A. & McNaughton, B. L. Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993)

    Article  ADS  CAS  Google Scholar 

  28. Mountcastle, V. B. The columnar organization of the neocortex. Brain 120, 701–722 (1997)

    Article  Google Scholar 

  29. Rockland, K. S. & Ichinohe, N. Some thoughts on cortical minicolumns. Exp. Brain Res. 158, 265–277 (2004)

    Article  Google Scholar 

  30. Ikeda, J., Mori, K., Oka, S. & Watanabe, Y. A columnar arrangement of dendritic processes of entorhinal cortex neurons revealed by a monoclonal antibody. Brain Res. 505, 176–179 (1989)

    Article  CAS  Google Scholar 

  31. Quirk, G. J., Muller, R. U., Kubie, J. L. & Ranck, J. B. Jr The positional firing properties of medial entorhinal neurons: description and comparison with hippocampal place cells. J. Neurosci 12, 1945–1963 (1992)

    Article  CAS  Google Scholar 

  32. Taube, J. S., Muller, R. U. & Ranck, J. B. Jr Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations. J. Neurosci. 10, 436–447 (1990)

    Article  CAS  Google Scholar 

  33. Goodridge, J. P. & Taube, J. S. Preferential use of the landmark navigational system by head direction cells in rats. Behav. Neurosci. 109, 49–61 (1995)

    Article  CAS  Google Scholar 

  34. Mittelstaedt, M. L. & Mittelstaedt, H. Homing by path integration in a mammal. Naturwissenschaften 67, 566–567 (1980)

    Article  ADS  Google Scholar 

  35. Gallistel, C. R. The Organization of Learning (MIT Press, Cambridge Massachusetts, 1990)

    Google Scholar 

  36. Biegler, R. Possible uses of path integration in animal navigation. Anim. Learn. Behav. 28, 257–277 (2000)

    Article  Google Scholar 

  37. van Haeften, T., Wouterlood, F. G., Jorritsma-Byham, B. & Witter, M. P. GABAergic presubicular projections to the medial entorhinal cortex of the rat. J. Neurosci. 17, 862–874 (1997)

    Article  CAS  Google Scholar 

  38. Witter, M. P., Groenewegen, H. J., Lopes da Silva, F. H. & Lohman, A. H. Functional organization of the extrinsic and intrinsic circuitry of the parahippocampal region. Prog. Neurobiol. 33, 161–253 (1989)

    Article  CAS  Google Scholar 

  39. Witter, M. P. & Amaral, D. G. in The Rat Nervous System 3rd edn (ed. Paxinos, G.) 637–703 (Academic, San Diego, 2004)

    Google Scholar 

  40. Parron, C. & Save, E. Evidence for entorhinal and parietal cortices involvement in path integration in the rat. Exp. Brain Res. 159, 349–359 (2004)

    Article  Google Scholar 

  41. Steffenach, H.-A., Witter, M. P., Moser, M.-B. & Moser, E. I. Spatial memory in the rat requires the dorsolateral band of the entorhinal cortex. Neuron 45, 301–313 (2005)

    Article  CAS  Google Scholar 

  42. Skaggs, W. E., Knierim, J. J., Kudrimoto, H. & McNaughton, B. L. in Advances in Neural Information Processing Systems (eds Tesauro, G., Touretzky, D. S. & Leen, T. K.) Vol. 7, 173–180 (MIT Press, Cambridge, Massachusetts, 1995)

    Google Scholar 

  43. Lingenhohl, K. & Finch, D. M. Morphological characterization of rat entorhinal neurons in vivo: soma-dendritic structure and axonal domains. Exp. Brain Res. 84, 57–74 (1991)

    Article  CAS  Google Scholar 

  44. Germroth, P., Schwerdtfeger, W. K. & Buhl, E. H. Ultrastructure and aspects of functional organization of pyramidal and nonpyramidal entorhinal projection neurons contributing to the perforant path. J. Comp. Neurol. 305, 215–231 (1991)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  46. Egorov, A. V., Hamam, B. N., Fransen, E., Hasselmo, M. E. & Alonso, A. A. Graded persistent activity in entorhinal cortex neurons. Nature 420, 173–178 (2002)

    Article  ADS  CAS  Google Scholar 

  47. Iijima, T. et al. Entorhinal-hippocampal interactions revealed by real-time imaging. Science 272, 1176–1179 (1996)

    Article  ADS  CAS  Google Scholar 

  48. Lorincz, A. & Buzsaki, G. Two-phase computational model training long-term memories in the entorhinal-hippocampal region. Ann. NY Acad. Sci. 911, 83–111 (2000)

    Article  ADS  CAS  Google Scholar 

  49. Fyhn, M., Molden, S., Hollup, S., Moser, M.-B. & Moser, E. I. Hippocampal neurons responding to first-time dislocation of a target object. Neuron 35, 555–566 (2002)

    Article  CAS  Google Scholar 

  50. Sargolini, F., Molden, S., Witter, M. P., Moser, E. I. & Moser, M.-B. Place representation in the deep layers of entorhinal cortex. Soc. Neurosci. Abstr. 30, 330.9 (2004)

    Google Scholar 

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We are grateful to the members of the Centre for the Biology of Memory as well as W. E. Skaggs, J. Lisman and G. Einevoll for discussions. We also thank the technical team of the Centre for their assistance. This work is supported by the Norwegian Research Council's Centre of Excellence scheme.

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Correspondence to Edvard I. Moser.

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Supplementary information

Supplementary Methods

Supplementary Methods (pdf format), including procedures for computation of spatial autocorrelations and cross-correlations. (PDF 36 kb)

Supplementary Figure S1

Temporal autocorrelation diagrams and spatial autocorrelation diagrams for scrambled rate maps. (PDF 243 kb)

Supplementary Figure S2

Trajectory and rate maps showing that grid vertices are stable across trials. (PDF 1308 kb)

Supplementary Figure S3

Trajectory and rate maps showing preserved grid spacing after scaling of the environment. (PDF 1165 kb)

Supplementary Figure S4

Grids recorded at different dorsoventral positions in dMEC. (PDF 2022 kb)

Supplementary Figure S5

Spatial cross-correlations between cells recorded simultaneously from areas with different grid spacing. (PDF 882 kb)

Supplementary Figure S6

Cue rotation experiment showing alignment of firing grids to environment-specific landmarks (PDF 482 kb)

Supplementary Figure S7

Trajectory and rate maps showing maintained grid structure after onset of darkness. (PDF 1949 kb)

Supplementary Figure S8

Trajectory with spikes in a rat running on a linear track in darkness. (PDF 198 kb)

Supplementary Figure S9

Parallel recording of entorhinal grid cells and hippocampal place cells (area CA3). (PDF 1172 kb)

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Hafting, T., Fyhn, M., Molden, S. et al. Microstructure of a spatial map in the entorhinal cortex. Nature 436, 801–806 (2005).

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