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The grid code for ordered experience

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.

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

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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.

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

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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.

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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

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