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Intracellular dynamics of hippocampal place cells during virtual navigation

Abstract

Hippocampal place cells encode spatial information in rate and temporal codes. To examine the mechanisms underlying hippocampal coding, here we measured the intracellular dynamics of place cells by combining in vivo whole-cell recordings with a virtual-reality system. Head-restrained mice, running on a spherical treadmill, interacted with a computer-generated visual environment to perform spatial behaviours. Robust place-cell activity was present during movement along a virtual linear track. From whole-cell recordings, we identified three subthreshold signatures of place fields: an asymmetric ramp-like depolarization of the baseline membrane potential, an increase in the amplitude of intracellular theta oscillations, and a phase precession of the intracellular theta oscillation relative to the extracellularly recorded theta rhythm. These intracellular dynamics underlie the primary features of place-cell rate and temporal codes. The virtual-reality system developed here will enable new experimental approaches to study the neural circuits underlying navigation.

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Figure 1: Predicted and measured subthreshold membrane potential dynamics during a run through a cell’s place field.
Figure 2: Spatial behaviours in a virtual-reality environment.
Figure 3: Extracellular recordings of CA1 place cells along the virtual linear track.
Figure 4: Ramp-like membrane potential depolarization inside place fields.
Figure 5: Membrane potential theta oscillations in place cells.

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Acknowledgements

We thank E. Chaffin for help with mouse behaviour, J. Carmack and id Software for providing the Quake2 code, A. Shishlov for programming advice, G. Buzsaki, J. Magee, H. Dahmen and D. Markowitz for discussions, and C. Brody, M. Berry and E. Civillico for comments on the manuscript. This work was supported by the NIH (1R01MH083686-01, 5R01MH060651-09), a Helen Hay Whitney Fellowship (to C.D.H.), and a Patterson Trust Fellowship (to D.A.D.).

Author Contributions C.D.H. performed behaviour and intracellular recording experiments with technical assistance from D.A.D. C.D.H. and D.A.D. performed extracellular recording experiments. F.C., D.A.D. and D.W.T. designed, and C.D.H., F.C. and D.W.T. implemented, the virtual-reality instrumentation. F.C. performed virtual-reality software development. C.D.H. analysed all data with strategy and methods contributions from all authors. C.D.H. and D.W.T. wrote the paper.

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Correspondence to David W. Tank.

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Harvey, C., Collman, F., Dombeck, D. et al. Intracellular dynamics of hippocampal place cells during virtual navigation. Nature 461, 941–946 (2009). https://doi.org/10.1038/nature08499

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