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.

Hippocampal remapping and grid realignment in entorhinal cortex

Nature volume 446, pages 190–194 (2007)Cite this article

Abstract

A fundamental property of many associative memory networks is the ability to decorrelate overlapping input patterns before information is stored1,2,3,4,5. In the hippocampus, this neuronal pattern separation is expressed as the tendency of ensembles of place cells6 to undergo extensive ‘remapping’ in response to changes in the sensory or motivational inputs to the hippocampus7,8,9,10,11,12,13. Remapping is expressed under some conditions as a change of firing rates in the presence of a stable place code (‘rate remapping’)14, and under other conditions as a complete reorganization of the hippocampal place code in which both place and rate of firing take statistically independent values (‘global remapping’)14. Here we show that the nature of hippocampal remapping can be predicted by ensemble dynamics in place-selective grid cells in the medial entorhinal cortex15,16, one synapse upstream of the hippocampus. Whereas rate remapping is associated with stable grid fields, global remapping is always accompanied by a coordinate shift in the firing vertices of the grid cells. Grid fields of co-localized medial entorhinal cortex cells move and rotate in concert during this realignment. In contrast to the multiple environment-specific representations coded by place cells in the hippocampus, local ensembles of grid cells thus maintain a constant spatial phase structure, allowing position to be represented and updated by the same translation mechanism in all environments encountered by the animal.

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

Relevant articles

Open Access articles citing this article.

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

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

Figure 1: Procedures for inducing global remapping and rate remapping in hippocampal area CA3.
Figure 2: Realignment of entorhinal grid fields during hippocampal global remapping between different boxes in the same location.
Figure 3: Realignment of entorhinal grid fields during hippocampal global remapping between two rooms.
Figure 4: Unaltered alignment of entorhinal grid fields during rate remapping in CA3.

References

  1. Marr, D. Simple memory: a theory of archicortex. Phil. Trans. R. Soc. Lond. B 262, 23–81 (1971)

    Article  ADS  CAS  Google Scholar 

  2. McNaughton, B. L. & Nadel, L. in Neuroscience and Connectionist Theory (eds Gluck, M. A. & Rumelhart, D. E.) 1–63 (Erlbaum, Hillsdale, NJ, 1989)

    Google Scholar 

  3. Treves, A. & Rolls, E. T. Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network. Hippocampus 2, 189–199 (1992)

    Article  CAS  Google Scholar 

  4. Kesner, R. P., Gilbert, P. E. & Wallenstein, G. V. Testing neural network models of memory with behavioral experiments. Curr. Opin. Neurobiol. 10, 260–265 (2000)

    Article  CAS  Google Scholar 

  5. Leutgeb, S., Leutgeb, J. K., Moser, M.-B. & Moser, E. I. Place cells, spatial maps and the population code for memory. Curr. Opin. Neurobiol. 15, 738–746 (2005)

    Article  CAS  Google Scholar 

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

    Google Scholar 

  7. 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 

  8. 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 

  9. Kentros, C. et al. Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science 280, 2121–2126 (1998)

    Article  ADS  CAS  Google Scholar 

  10. 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 

  11. 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 

  12. Lever, C., Wills, T., Cacucci, F., Burgess, N. & O’Keefe, J. Long-term plasticity in hippocampal place-cell representation of environmental geometry. Nature 416, 90–94 (2002)

    Article  ADS  CAS  Google Scholar 

  13. 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 

  14. Leutgeb, S. et al. Independent codes for spatial and episodic memory in the hippocampus. Science 309, 619–623 (2005)

    Article  ADS  CAS  Google Scholar 

  15. 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 

  16. 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  ADS  CAS  Google Scholar 

  17. 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 

  18. Sargolini, F. et al. Conjunctive representation of position, direction and velocity in entorhinal cortex. Science 312, 754–758 (2006)

    Article  ADS  Google Scholar 

  19. 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 

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

    Article  Google Scholar 

  21. Wills, T. J., Lever, C., Cacucci, F., Burgess, N. & O’Keefe, J. Attractor dynamics in the hippocampal representation of the local environment. Science 308, 873–876 (2005)

    Article  ADS  CAS  Google Scholar 

  22. Anderson, M. I. & Jeffery, K. J. Heterogeneous modulation of place cell firing by changes in context. J. Neurosci. 23, 8827–8835 (2003)

    Article  CAS  Google Scholar 

  23. Quirk, G. J., Muller, R. U. & Kubie, J. L. The firing of hippocampal place cells in the dark depends on the rat’s recent experience. J. Neurosci. 10, 2008–2017 (1990)

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  25. 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 

  26. 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 

  27. Leutgeb, J. K., Leutgeb, S., Moser, M.-B. & Moser, E. I. Pattern separation in dentate gyrus and CA3 of the hippocampus. Science 315 doi: 10.1126/science.1135801 (16 February 2007)

  28. Hargreaves, E. L., Rao, G., Lee, I. & Knierim, J. J. Major dissociation between medial and lateral entorhinal input to the dorsal hippocampus. Science 308, 1792–1794 (2005)

    Article  ADS  CAS  Google Scholar 

  29. Naber, P. A., Caballero-Bleda, M., Jorritsma-Byham, B. & Witter, M. P. Parallel input to the hippocampal memory system through peri- and postrhinal cortices. Neuroreport 8, 2617–2621 (1997)

    Article  CAS  Google Scholar 

  30. Battaglia, F. P. & Treves, A. Attractor neural networks storing multiple space representations: a model for hippocampal place fields. Phys. Rev. E Stat. Phys. Plasmas Fluids Relat. Interdiscip. Top. 58, 7738–7753 (1998)

    CAS  Google Scholar 

Download references

Acknowledgements

We thank S. Leutgeb, T. Solstad, B. L. McNaughton and M. P. Witter for discussion, R. Skjerpeng for programming, and I. Hammer, K. Haugen, K. Jenssen and H. Waade for technical assistance. This work was supported by a Centre of Excellence grant from the Norwegian Research Council.

Author Contributions M.F., T.H., M.-B.M. and E.I.M. planned experiments and analyses. M.F., T.H. and M.-B.M. performed the experiments and analysed the data. A.T. gave advice on analyses, and E.I.M. wrote the paper. All authors discussed the results and contributed to the manuscript.

Author information

Author notes

  1. Marianne Fyhn and Torkel Hafting: These authors contributed equally to this work.

Authors and Affiliations

  1. Centre for the Biology of Memory, Norwegian University of Science and Technology, NO-7489 Trondheim, Norway,

    Marianne Fyhn, Torkel Hafting, Alessandro Treves, May-Britt Moser & Edvard I. Moser

  2. Cognitive Neuroscience Sector, SISSA International School for Advanced Studies, I-34014 Trieste, Italy,

    Alessandro Treves

Authors
  1. Marianne Fyhn
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Torkel Hafting
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alessandro Treves
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. May-Britt Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Edvard I. Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Edvard I. Moser.

Ethics declarations

Competing interests

Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures 1-12 with Legends, Supplementary Methods, Supplementary Tables 1-3, Supplementary Discussion and Supplementary Notes with additional references. Supplementary Figures 1-3 show representative recording locations in MEC and CA3, examples of global remapping and rate remapping in CA3 (rate maps for the complete cell sample in one animal and for all cells that were active in both environments in all animals), and crosscorrelation matrices for the entire set of grid-cell ensembles. Supplementary Figures 4-12 show additional crosscorrelations for individual cells and cell ensembles, simultaneous recordings from MEC and CA3, experiments addressing contiguity of grid realignment in MEC and global remapping in CA3, analyses of ensemble coactivity and rate distribution across grid vertices, and two models for global remapping in hippocampus during grid realignment in MEC. Supplementary Tables 1-3 show numbers of cells and experiments for individual rats, averaged firing properties of MEC and CA3 cells, and behavioural data. (PDF 9054 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fyhn, M., Hafting, T., Treves, A. et al. Hippocampal remapping and grid realignment in entorhinal cortex. Nature 446, 190–194 (2007). https://doi.org/10.1038/nature05601

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature05601

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

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