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Grid cells require excitatory drive from the hippocampus


To determine how hippocampal backprojections influence spatially periodic firing in grid cells, we recorded neural activity in the medial entorhinal cortex (MEC) of rats after temporary inactivation of the hippocampus. We report two major changes in entorhinal grid cells. First, hippocampal inactivation gradually and selectively extinguished the grid pattern. Second, the same grid cells that lost their grid fields acquired substantial tuning to the direction of the rat's head. This transition in firing properties was contingent on a drop in the average firing rate of the grid cells and could be replicated by the removal of an external excitatory drive in an attractor network model in which grid structure emerges by velocity-dependent translation of activity across a network with inhibitory connections. These results point to excitatory drive from the hippocampus, and possibly other regions, as one prerequisite for the formation and translocation of grid patterns in the MEC.

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Figure 1: Muscimol-induced inactivation of the dorsal hippocampus.
Figure 2: Disruption of entorhinal grid structure after inactivation of the hippocampus.
Figure 3: Disappearance of the grid pattern in dynamic maps.
Figure 4: Loss of grid structure leads to directional tuning.
Figure 5: Loss of the grid pattern depends on the decrease in firing rates of grid cells.
Figure 6: Remaining nonperiodic spatial firing after hippocampal inactivation.
Figure 7: Preserved theta activity during hippocampal inactivation.
Figure 8: The effect of hippocampus inactivation in an attractor model of grid cells.


  1. 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  CAS  PubMed  Google Scholar 

  2. 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  PubMed  Google Scholar 

  3. 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).

    CAS  PubMed  Google Scholar 

  4. 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  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  6. 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  CAS  PubMed  Google Scholar 

  7. 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  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  9. 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 

  10. 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  PubMed  Google Scholar 

  11. 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  PubMed  Google Scholar 

  12. 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  PubMed  PubMed Central  Google Scholar 

  13. Solstad, T., Moser, E.I. & Einevoll, G.T. From grid cells to place cells: a mathematical model. Hippocampus 16, 1026–1031 (2006).

    Article  PubMed  Google Scholar 

  14. Molter, C. & Yamaguchi, Y. Entorhinal theta phase precession sculpts dentate gyrus place fields. Hippocampus 18, 919–930 (2008).

    Article  PubMed  Google Scholar 

  15. Rolls, E.T., Stringer, S.M. & Elliot, T. Entorhinal cortex grid cells can map to hippocampal place cells by competitive learning. Network 17, 447–465 (2006).

    Article  PubMed  Google Scholar 

  16. de Almeida, L., Idiart, M. & Lisman, J.E. The input-output transformation of the hippocampal granule cells: from grid cells to place fields. J. Neurosci. 29, 7504–7512 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Savelli, F. & Knierim, J.J. Hebbian analysis of the transformation of medial entorhinal grid-cell inputs to hippocampal place fields. J. Neurophysiol. 103, 3167–3183 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Si, B. & Treves, A. The role of competitive learning in the generation of DG fields from EC inputs. Cogn. Neurodyn. 3, 177–187 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  19. 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); erratum 31, 11096 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. O'Keefe, J. & Burgess, N. Dual phase and rate coding in hippocampal place cells: theoretical significance and relationship to entorhinal grid cells. Hippocampus 15, 853–866 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  24. Samu, D., Erös, 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 

  25. 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  PubMed  Google Scholar 

  26. Allen, T.A. et al. Imaging the spread of reversible brain inactivations using fluorescent muscimol. J. Neurosci. Methods 171, 30–38 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Boccara, C.N. et al. Grid cells in pre- and parasubiculum. Nat. Neurosci. 13, 987–994 (2010).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  29. O'Keefe, J. & Recce, M.L. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993).

    Article  CAS  PubMed  Google Scholar 

  30. 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  Google Scholar 

  31. Couey, J.J. et al. Recurrent inhibitory circuitry as a mechanism for grid formation. Nat. Neurosci. doi:10.1038/nn.3310 (20 January 2013).

  32. van Haeften, T., Baks-te-Bulte, L., Goede, P.H., Wouterlood, F.G. & Witter, M.P. Morphological and numerical analysis of synaptic interactions between neurons in deep and superficial layers of the entorhinal cortex of the rat. Hippocampus 13, 943–952 (2003).

    Article  PubMed  Google Scholar 

  33. 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 

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

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. 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, 592–595 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. 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  CAS  PubMed  Google Scholar 

  37. Yoshida, M., Giocomo, L.G. & Hasselmo, M.E. Frequency of subthreshold oscillations at different membrane potential voltages in neurons at different anatomical positions on the dorsoventral axis in the rat medial entorhinal cortex. J. Neurosci. 31, 12683–12694 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. 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  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  40. 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  PubMed  Google Scholar 

  41. 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  PubMed  PubMed Central  Google Scholar 

  42. Burwell, R.D. & Hafeman, D.M. Positional firing properties of postrhinal cortex neurons. Neuroscience 119, 577–588 (2003).

    Article  CAS  PubMed  Google Scholar 

  43. Muller, R.U. & Kubie, J.L. The firing of hippocampal place cells predicts the future position of freely moving rat. J. Neurosci. 9, 4101–4110 (1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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We thank R. Skjerpeng for programming, M.P. Witter and C.B. Boccara for advice on tetrode locations, M. Mehta and M.P. Witter for discussion, N. Burgess for sharing code for dynamic autocorrelation analyses and A.M. Amundsgård, K. Haugen, K. Jenssen, E. Kråkvik and H. Waade for technical assistance. This work was supported by the Kavli Foundation, a studentship to T.B. from the Faculty of Medicine at NTNU, a Centre of Excellence grant from the Research Council of Norway and an Advanced Investigator Grant to E.I.M. from the European Research Council ('CIRCUIT', grant agreement 232608).

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Authors and Affiliations



T.B. and M.F. performed the majority of the experiments; T.B. did the majority of the analyses; B.D. and Y.R. did the network simulations; E.I.M. and T.B. wrote the manuscript, except for the computational model (B.D. and Y.R.); and M.-B.M. supervised the project. All authors contributed to discussion and interpretation.

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Correspondence to Edvard I Moser or May-Britt Moser.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–8 (PDF 9025 kb)

Supplementary Video 1

External input is large enough (100% hippocampal activity). This corresponds to an external input to the right of the transition in Fig. 8b. In this case, the activity on the neuronal sheet is a hexagonal grid. When the animal moves, this activity is translated on the network and follows the movement of the animal without being distorted. The resulting activity at the single cell levels is a hexagonal grid and thus high grid score. (MOV 22999 kb)

Supplementary Video 2

External input is below the transition. In this case, most of the time the activity on the neuronal sheet is still grid like, but the grid changes size, amplitude and orientation as it tries to follow the animals movement sometime turning into stripe patterns (see e.g. t = 0:16). The peak activity also substantially changes between different time steps. Consequently, no grid firing will be observed at the single cell level and substantially low grid scores are found. (MOV 23092 kb)

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

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