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The entorhinal grid map is discretized

Nature volume 492, pages 72–78 (2012)Cite this article

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Abstract

The medial entorhinal cortex (MEC) is part of the brain’s circuit for dynamic representation of self-location. The metric of this representation is provided by grid cells, cells with spatial firing fields that tile environments in a periodic hexagonal pattern. Limited anatomical sampling has obscured whether the grid system operates as a unified system or a conglomerate of independent modules. Here we show with recordings from up to 186 grid cells in individual rats that grid cells cluster into a small number of layer-spanning anatomically overlapping modules with distinct scale, orientation, asymmetry and theta-frequency modulation. These modules can respond independently to changes in the geometry of the environment. The discrete topography of the grid-map, and the apparent autonomy of the modules, differ from the graded topography of maps for continuous variables in several sensory systems, raising the possibility that the modularity of the grid map is a product of local self-organizing network dynamics.

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Figure 1: Step-like increases in grid scale along the entorhinal dorsoventral axis.
Figure 2: Comodular organization of grid orientation and grid scale.
Figure 3: Distortions in grid shape are comodular with grid spacing.
Figure 4: Grid modules are organized as overlapping horizontal bands.
Figure 5: Scale relationship between grid modules.
Figure 6: Comodularity between grid spacing and theta frequency.
Figure 7: Grid modules are functionally independent.

References

  1. Mountcastle, V. B. Modality and topographic properties of single neurons of cat’s somatic sensory cortex. J. Neurophysiol. 20, 408–434 (1957)

    Article  CAS  Google Scholar 

  2. Hubel, D. H. & Wiesel, T. Receptive fields, binocular interaction, and functional architecture of cat striate cortex. J. Physiol. (Lond.) 160, 106–154 (1962)

    Article  CAS  Google Scholar 

  3. Hubel, D. H. & Wiesel, T. Functional architecture of macaque monkey visual cortex. Proc. R. Soc. Lond. B Biol. Sci. 198, 1–59 (1977)

    Article  CAS  ADS  Google Scholar 

  4. Hubel, D. H. & Wiesel, T. Sequence regularity and geometry of orientation columns in the monkey striate cortex. J. Comp. Neurol. 158, 267–293 (1974)

    Article  CAS  Google Scholar 

  5. Blasdel, G. G. & Salama, G. Voltage sensitive dyes reveal a modular organization in monkey striate cortex. Nature 321, 579–585 (1986)

    Article  CAS  ADS  Google Scholar 

  6. Bonhoeffer, T. & Grinvald, A. Orientation columns in cat are organized in pin-wheel like patterns. Nature 353, 429–431 (1991)

    Article  CAS  ADS  Google Scholar 

  7. Ohki, K. et al. Highly ordered arrangement of single neurons in orientation pinwheels. Nature 442, 925–928 (2006)

    Article  CAS  ADS  Google Scholar 

  8. Payne, B. R., Berman, N. & Murphy, E. H. Organization of direction preferences in cat visual cortex. Brain Res. 211, 445–450 (1981)

    Article  CAS  Google Scholar 

  9. Tolhurst, D. J., Dean, A. F. & Thompson, I. D. Preferred direction of movement as an element in the organization of cat visual cortex. Exp. Brain Res. 44, 340–342 (1981)

    Article  CAS  Google Scholar 

  10. Weliky, M., Bosking, W. H. & Fitzpatrick, D. A systematic map of direction preference in primary visual cortex. Nature 379, 725–728 (1996)

    Article  CAS  ADS  Google Scholar 

  11. Ohki, K., Chung, S., Ch’ng, Y. H., Kara, P. & Reid, R. C. Functional imaging with cellular resolution reveals precise micro-architecture in visual cortex. Nature 433, 597–603 (2005)

    Article  CAS  ADS  Google Scholar 

  12. Sperry, R. W. Visuomotor coordination in the newt (Triturus viridescens) after regeneration of the optic nerve. J. Comp. Neurol. 79, 33–55 (1943)

    Article  Google Scholar 

  13. Drescher, U. et al. In vitro guidance of retinal ganglion cell axons by RAGS, a 25 kDa tectal protein related to ligands for Eph receptor tyrosine kinases. Cell 82, 359–370 (1995)

    Article  CAS  Google Scholar 

  14. Cheng, H. J., Nakamoto, M., Bergemann, A. D. & Flanagan, J. G. Complementary gradients in expression and binding of ELF-1 and Mek4 in development of the topographic retinotectal projection map. Cell 82, 371–381 (1995)

    Article  CAS  Google Scholar 

  15. 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  Google Scholar 

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

    Google Scholar 

  17. Moser, E. I., Kropff, E. & Moser, M.-B. Place cells, grid cells, and the brain’s spatial representation system. Annu. Rev. Neurosci. 31, 69–89 (2008)

    Article  CAS  Google Scholar 

  18. 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  CAS  ADS  Google Scholar 

  19. 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  CAS  ADS  Google Scholar 

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

    Article  CAS  ADS  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’. Nature Rev. Neurosci. 7, 663–678 (2006)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  23. 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  CAS  Google Scholar 

  24. Burgess, N., Barry, C. & O’Keefe, J. An oscillatory interference model of grid cell firing. Hippocampus 17, 801–812 (2007)

    Article  Google Scholar 

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

    Article  Google Scholar 

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

    Article  ADS  MathSciNet  Google Scholar 

  27. Zilli, E. A. & Hasselmo, M. E. Coupled noisy spiking neurons as velocity-controlled oscillators in a model of grid cell spatial firing. J. Neurosci. 30, 13850–13860 (2010)

    Article  CAS  Google Scholar 

  28. Mhatre, H., Gorchetchnikov, A. & Grossberg, S. Grid cell hexagonal patterns formed by fast self-organized learning within entorhinal cortex. Hippocampus 22, 320–334 (2012)

    Article  Google Scholar 

  29. Witter, M. P. & Moser, E. I. Spatial representation and the architecture of the entorhinal cortex. Trends Neurosci. 29, 671–678 (2006)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  31. 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  CAS  ADS  Google Scholar 

  32. Brun, V. H. et al. Progressive increase in grid scale from dorsal to ventral medial entorhinal cortex. Hippocampus 18, 1200–1212 (2008)

    Article  MathSciNet  Google Scholar 

  33. 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  CAS  ADS  Google Scholar 

  34. Jeewajee, A., Barry, C., O’Keefe, J. & Burgess, N. Grid cells and theta as oscillatory interference: electrophysiological data from freely moving rats. Hippocampus 18, 1175–1185 (2008)

    Article  CAS  Google Scholar 

  35. 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  CAS  ADS  Google Scholar 

  36. 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  CAS  ADS  Google Scholar 

  37. Krupic, J., Burgess, N. & O’Keefe, J. Neural representations of location composed of spatially periodic bands. Science 337, 853–857 (2012)

    Article  CAS  ADS  Google Scholar 

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

    Article  CAS  ADS  Google Scholar 

  39. Hevner, R. F. & Wong-Riley, M. T. Entorhinal cortex of the human, monkey, and rat: metabolic map as revealed by cytochrome oxidase. J. Comp. Neurol. 326, 451–469 (1992)

    Article  CAS  Google Scholar 

  40. Burgalossi, A. et al. Microcircuits of functionally identified neurons in the rat medial entorhinal cortex. Neuron 70, 773–786 (2011)

    Article  CAS  Google Scholar 

  41. Ikeda, J., Mori, K., Oka, S. & Watanbe, 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 

  42. Couey, J. J. et al. Medical entorhinal cortex layer ii stellate cells are embedded within a recurrent inhibitory network. Soc. Necuosci. abstr. 702.06 (2012)

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

    Article  CAS  ADS  Google Scholar 

  44. 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  CAS  ADS  Google Scholar 

  45. Hasselmo, M. E., Giocomo, L. M. & Zilli, E. A. Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons. Hippocampus 17, 1252–1271 (2007)

    Article  Google Scholar 

  46. Blair, H. T., Welday, A. C. & Zhang, K. Scale-invariant memory representations emerge from moiré interference between grid fields that produce theta oscillations: a computational model. J. Neurosci. 27, 3211–3229 (2007)

    Article  CAS  Google Scholar 

  47. Sreenivasan, S. & Fiete, I. Grid cells generate an analog error-correcting code for singularly precise neural computation. Nature Neurosci. 14, 1330–1337 (2011)

    Article  CAS  Google Scholar 

  48. Monaco, J. D. & Abbott, L. F. Modular realignment of entorhinal grid cell activity as a basis for hippocampal remapping. J. Neurosci. 31, 9414–9425 (2011)

    Article  CAS  Google Scholar 

  49. 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 

  50. Colgin, L. L., Moser, E. I. & Moser, M.-B. Understanding memory through hippocampal remapping. Trends Neurosci. 31, 469–477 (2008)

    Article  CAS  Google Scholar 

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Acknowledgements

We thank A. M. Amundgård, K. Haugen, K. Jenssen, E. Kråkvik, R. Skjerpeng, and H. Waade for technical assistance, J. Whitlock for implanting an animal in the tangential group, and T. Bonhoeffer, B. Dunn, B. McNaughton, Y. Roudi, A. Treves and A. Witoelar for helpful discussion. The work was supported by an Advanced Investigator Grant from the European Research Council (‘CIRCUIT’, Grant Agreement no. 232608), the Kavli Foundation and the Centre of Excellence scheme of the Research Council of Norway.

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  1. Hanne Stensola and Tor Stensola: These authors contributed equally to this work.

Authors and Affiliations

  1. Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory, Norwegian University of Science and Technology, Olav Kyrres gate 9, MTFS, 7491 Trondheim, Norway,

    Hanne Stensola, Tor Stensola, Trygve Solstad, Kristian Frøland, May-Britt Moser & Edvard I. Moser

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Contributions

T.St., H.S., T.So., M.-B.M. and E.I.M. designed experiments and analyses; H.S., T.St. and T.So. implanted tetrodes; H.S. recorded multisite data; T.So. and K.F. tested animals with tangential implants; T.St. performed the majority of the analyses; and T.St. and E.I.M. wrote the paper with input from all authors.

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Correspondence to Hanne Stensola, Tor Stensola or Edvard I. Moser.

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Stensola, H., Stensola, T., Solstad, T. et al. The entorhinal grid map is discretized. Nature 492, 72–78 (2012). https://doi.org/10.1038/nature11649

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