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Grid cells require excitatory drive from the hippocampus

Nature Neuroscience volume 16, pages 309–317 (2013)Cite this article

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Abstract

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.

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Acknowledgements

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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Author notes

  1. Marianne Fyhn, Torkel Hafting & Dori Derdikman

    Present address: Present addresses: Department of Molecular Biosciences, University of Oslo, Kristine Bonnevies hus, Oslo, Norway (M.F. & T.H.) and Technion, Israel Institute of Technology, Rappaport Faculty of Medicine, Bat Galim, Haifa, Israel (D.D.).,

Authors and Affiliations

  1. Kavli Institute for Systems Neuroscience and Centre for the Biology of Memory, Norwegian Brain Centre, Norwegian University of Science and Technology (NTNU), Trondheim, Norway

    Tora Bonnevie, Benjamin Dunn, Marianne Fyhn, Torkel Hafting, Dori Derdikman, Yasser Roudi, Edvard I Moser & May-Britt Moser

  2. Department of Cell Biology, State University of New York Downstate Medical Center, Brooklyn, New York, USA

    John L Kubie

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Contributions

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). https://doi.org/10.1038/nn.3311

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