Abstract
Neurons in the medial entorhinal cortex exhibit a grid-like spatial pattern of spike rates that has been proposed to represent a neural code for path integration. To understand how grid cell firing arises from the combination of intrinsic conductances and synaptic input in medial entorhinal stellate cells, we performed patch-clamp recordings in mice navigating in a virtual-reality environment. We found that the membrane potential signature of stellate cells during firing field crossings consisted of a slow depolarization driving spike output. This was best predicted by network models in which neurons receive sustained depolarizing synaptic input during a field crossing, such as continuous attractor network models of grid cell firing. Another key feature of the data, phase precession of intracellular theta oscillations and spiking with respect to extracellular theta oscillations, was best captured by an oscillatory interference model. Thus, these findings provide crucial new information for a quantitative understanding of the cellular basis of spatial navigation in the entorhinal cortex.
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Acknowledgements
We are grateful to N. Burgess, B. Clark, P. Dayan, K. Harris, P. Latham, J. O'Keefe, A. Packer, A. Roth, S. Turaga and C. Wilms for helpful discussions and for comments on the manuscript, and to A. Naeem for assistance with histology. This work was supported by grants from the Wellcome Trust, European Research Council and Gatsby Charitable Foundation, and by a fellowship to C. S.-H. from the Alexander von Humboldt Foundation.
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C.S.-H. and M.H. designed the study, interpreted the results and wrote the paper. C.S.-H. performed the experiments, analysis and modeling.
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Supplementary Text and Figures
Supplementary Figures 1–10 and Supplementary Table 1 (PDF 13164 kb)
Supplementary Video 1
Video of mouse navigation in virtual reality (MP4 5403 kb)
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Schmidt-Hieber, C., Häusser, M. Cellular mechanisms of spatial navigation in the medial entorhinal cortex. Nat Neurosci 16, 325–331 (2013). https://doi.org/10.1038/nn.3340
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DOI: https://doi.org/10.1038/nn.3340
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