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Hippocampus-independent phase precession in entorhinal grid cells

Nature volume 453, pages 1248–1252 (2008)Cite this article

Abstract

Theta-phase precession in hippocampal place cells1 is one of the best-studied experimental models of temporal coding in the brain. Theta-phase precession is a change in spike timing in which the place cell fires at progressively earlier phases of the extracellular theta rhythm as the animal crosses the spatially restricted firing field of the neuron1,2,3,4,5. Within individual theta cycles, this phase advance results in a compressed replication of the firing sequence of consecutively activated place cells along the animal’s trajectory2,6,7,8, at a timescale short enough to enable spike-time-dependent plasticity between neurons in different parts of the sequence. The neuronal circuitry required for phase precession has not yet been established. The fact that phase precession can be seen in hippocampal output stuctures such as the prefrontal cortex9 suggests either that efferent structures inherit the precession from the hippocampus or that it is generated locally in those structures. Here we show that phase precession is expressed independently of the hippocampus in spatially modulated grid cells10,11 in layer II of medial entorhinal cortex, one synapse upstream of the hippocampus. Phase precession is apparent in nearly all principal cells in layer II but only sparsely in layer III. The precession in layer II is not blocked by inactivation of the hippocampus, suggesting that the phase advance is generated in the grid cell network. The results point to possible mechanisms for grid formation and raise the possibility that hippocampal phase precession is inherited from entorhinal cortex.

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Figure 1: Phase precession in a layer II cell in MEC.
Figure 2: Phase locking in layer III of MEC.
Figure 3: Population data.
Figure 4: Phase precession in entorhinal cortex after inactivation of the hippocampus.

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Acknowledgements

We thank R. Skjerpeng for programming; M. P. Witter for advice on electrode localization; A. Treves for statistical advice; A. M. Amundsgaard, D. Derdikman, K. Haugen, K. Jenssen, E. Sjulstad and H. Waade for technical or other assistance; and several colleagues for discussion. The work was supported by the Kavli Foundation, a Centre of Excellence grant from the Norwegian Research Council and the 2006 Life Science award of the Fondation Bettencourt Schueller.

Author Contributions T.H., M.F., M.-B.M. and E.I.M. planned the experiments; T.H., M.F., T.B. and M.-B.M. performed the experiments; all authors analysed the data; and E.I.M. wrote the paper. All authors discussed the results and contributed to the manuscript. M.F. and T.H. contributed equally.

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Author notes

  1. Torkel Hafting and Marianne Fyhn: 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, NO-7489 Trondheim, Norway

    Torkel Hafting, Marianne Fyhn, Tora Bonnevie, May-Britt Moser & Edvard I. Moser

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  1. Torkel Hafting
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  2. Marianne Fyhn
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  3. Tora Bonnevie
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  4. May-Britt Moser
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Corresponding author

Correspondence to Edvard I. Moser.

Supplementary information

Supplementary Figures 1-8

The file contains Supplementary Figures 1-8 and Legends. Recording locations in layers II and III of MEC, additional examples of phase modulation in layers II and III of MEC and CA3 and CA1 of the hippocampus, simultaneously recorded data from layers II and III, coherence of theta field oscillations between layers II and III of MEC, firing rate as a function of theta phase, and distribution of phase relationships across 20% segments of the firing fields in each recording area. (PDF 8002 kb)

Supplementary Figures 9-13

The file contains Supplementary Figures 9-13 and Legends. Firing phase as a function of time after entering the firing field, layer II fields with positive position-phase regression lines, change in rate of phase precession along the dorsoventral axis of MEC, phase precession in layer V of MEC, and phase relationships of cells in the layer III – layer II transition zone. (PDF 6128 kb)

Supplementary Figures 14-18

The file contains Supplementary Figures 14-18 and Legends. Recording and infusion locations and hippocampal inactivation curves for phase precession experiments with muscimol infusions into the hippocampus, group data and individual examples showing asymmetry and experience-dependent shifts in firing locations of grid cells and place cells, and examples and analyses showing lack of relation between phase precession and experience-dependent changes in field shape or field size in grid cells. (PDF 3279 kb)

Supplementary Methods

The file contains Supplementary Methods. (PDF 214 kb)

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Hafting, T., Fyhn, M., Bonnevie, T. et al. Hippocampus-independent phase precession in entorhinal grid cells. Nature 453, 1248–1252 (2008). https://doi.org/10.1038/nature06957

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