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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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.

References

  1. 1

    Moser, E. I., Kropff, E. & Moser, M. B. Place cells, grid cells, and the brain’s spatial representation system. Annu. Rev. Neurosci. 31, 69–89 (2008)

  2. 2

    O’Keefe, J. & Burgess, N. Dual phase and rate coding in hippocampal place cells: theoretical significance and relationship to entorhinal grid cells. Hippocampus 15, 853–866 (2005)

  3. 3

    O’Keefe, J. & Dostrovsky, J. The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat. Brain Res. 34, 171–175 (1971)

  4. 4

    O’Keefe, J. & Recce, M. L. Phase relationship between hippocampal place units and the EEG theta rhythm. Hippocampus 3, 317–330 (1993)

  5. 5

    Skaggs, W. E., McNaughton, B. L., Wilson, M. A. & Barnes, C. A. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996)

  6. 6

    Buzsáki, G. Theta oscillations in the hippocampus. Neuron 33, 325–340 (2002)

  7. 7

    Tsodyks, M. V., Skaggs, W. E., Sejnowski, T. J. & McNaughton, B. L. Population dynamics and theta rhythm phase precession of hippocampal place cell firing: a spiking neuron model. Hippocampus 6, 271–280 (1996)

  8. 8

    Jensen, O. & Lisman, J. E. Hippocampal CA3 region predicts memory sequences: accounting for the phase precession of place cells. Learn. Mem. 3, 279–287 (1996)

  9. 9

    Wallenstein, G. V. & Hasselmo, M. E. GABAergic modulation of hippocampal population activity: sequence learning, place field development, and the phase precession effect. J. Neurophysiol. 78, 393–408 (1997)

  10. 10

    Kamondi, A., Acsady, L., Wang, X. J. & Buzsaki, G. Theta oscillations in somata and dendrites of hippocampal pyramidal cells in vivo: activity-dependent phase-precession of action potentials. Hippocampus 8, 244–261 (1998)

  11. 11

    Magee, J. C. Dendritic mechanisms of phase precession in hippocampal CA1 pyramidal neurons. J. Neurophysiol. 86, 528–532 (2001)

  12. 12

    Mehta, M. R., Lee, A. K. & Wilson, M. A. Role of experience and oscillations in transforming a rate code into a temporal code. Nature 417, 741–746 (2002)

  13. 13

    Harris, K. D. et al. Spike train dynamics predicts theta-related phase precession in hippocampal pyramidal cells. Nature 417, 738–741 (2002)

  14. 14

    Lengyel, M., Szatmary, Z. & Erdi, P. Dynamically detuned oscillations account for the coupled rate and temporal code of place cell firing. Hippocampus 13, 700–714 (2003)

  15. 15

    Gasparini, S. & Magee, J. C. State-dependent dendritic computation in hippocampal CA1 pyramidal neurons. J. Neurosci. 26, 2088–2100 (2006)

  16. 16

    Maurer, A. P. & McNaughton, B. L. Network and intrinsic cellular mechanisms underlying theta phase precession of hippocampal neurons. Trends Neurosci. 30, 325–333 (2007)

  17. 17

    Lee, A. K., Manns, I. D., Sakmann, B. & Brecht, M. Whole-cell recordings in freely moving rats. Neuron 51, 399–407 (2006)

  18. 18

    Lee, A. K., Epsztein, J. & Brecht, M. Head-anchored whole-cell recordings in freely moving rats. Nature Protocols 4, 385–392 (2009)

  19. 19

    Dombeck, D. A., Khabbaz, A. N., Collman, F., Adelman, T. L. & Tank, D. W. Imaging large-scale neural activity with cellular resolution in awake, mobile mice. Neuron 56, 43–57 (2007)

  20. 20

    Hölscher, C., Schnee, A., Dahmen, H., Setia, L. & Mallot, H. A. Rats are able to navigate in virtual environments. J. Exp. Biol. 208, 561–569 (2005)

  21. 21

    Chahl, J. S. & Srinivasan, M. V. Reflective surfaces for panoramic imaging. Appl. Opt. 36, 8275–8285 (1997)

  22. 22

    Ranck, J. B. Studies on single neurons in dorsal hippocampal formation and septum in unrestrained rats. I. Behavioral correlates and firing repertoires. Exp. Neurol. 41, 461–531 (1973)

  23. 23

    Kandel, E. R. & Spencer, W. A. Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. J. Neurophysiol. 24, 243–259 (1961)

  24. 24

    Quirk, M. C. & Wilson, M. A. Interaction between spike waveform classification and temporal sequence detection. J. Neurosci. Methods 94, 41–52 (1999)

  25. 25

    McNaughton, B. L., Barnes, C. A. & O’Keefe, J. The contributions of position, direction, and velocity to single unit activity in the hippocampus of freely-moving rats. Exp. Brain Res. 52, 41–49 (1983)

  26. 26

    Nakazawa, K. et al. Hippocampal CA3 NMDA receptors are crucial for memory acquisition of one-time experience. Neuron 38, 305–315 (2003)

  27. 27

    Kentros, C. G., Agnihotri, N. T., Streater, S., Hawkins, R. D. & Kandel, E. R. Increased attention to spatial context increases both place field stability and spatial memory. Neuron 42, 283–295 (2004)

  28. 28

    Cacucci, F., Wills, T. J., Lever, C., Giese, K. P. & O’Keefe, J. Experience-dependent increase in CA1 place cell spatial information, but not spatial reproducibility, is dependent on the autophosphorylation of the alpha-isoform of the calcium/calmodulin-dependent protein kinase II. J. Neurosci. 27, 7854–7859 (2007)

  29. 29

    Sun, L. D. & Wilson, M. A. Impaired and Enhanced Spatial Representations of the PSD-95 Knockout Mouse. PhD thesis, Massachusetts Institute of Technology. (2003)

  30. 30

    Margrie, T. W., Brecht, M. & Sakmann, B. In vivo, low-resistance, whole-cell recordings from neurons in the anaesthetized and awake mammalian brain. Pflugers Arch. 444, 491–498 (2002)

  31. 31

    Crochet, S. & Petersen, C. C. Correlating whisker behavior with membrane potential in barrel cortex of awake mice. Nature Neurosci. 9, 608–610 (2006)

  32. 32

    Wilson, M. A. & McNaughton, B. L. Dynamics of the hippocampal ensemble code for space. Science 261, 1055–1058 (1993)

  33. 33

    Guzowski, J. F., McNaughton, B. L., Barnes, C. A. & Worley, P. F. Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nature Neurosci. 2, 1120–1124 (1999)

  34. 34

    Henze, D. A. et al. Intracellular features predicted by extracellular recordings in the hippocampus in vivo . J. Neurophysiol. 84, 390–400 (2000)

  35. 35

    Kandel, E. R. & Spencer, W. A. Electrophysiology of hippocampal neurons. IV. Fast prepotentials. J. Neurophysiol. 24, 272–285 (1961)

  36. 36

    Wong, R. K. & Prince, D. A. Participation of calcium spikes during intrinsic burst firing in hippocampal neurons. Brain Res. 159, 385–390 (1978)

  37. 37

    Hafting, T., Fyhn, M., Bonnevie, T., Moser, M. B. & Moser, E. I. Hippocampus-independent phase precession in entorhinal grid cells. Nature 453, 1248–1252 (2008)

  38. 38

    Greene, N. Environment mapping and other applications of world projections. IEEE Comput. Graph. Appl. 6, 21–29 (1986)

  39. 39

    Wong, A. A. & Brown, R. E. Visual detection, pattern discrimination and visual acuity in 14 strains of mice. Genes Brain Behav. 5, 389–403 (2006)

  40. 40

    Rinberg, D., Koulakov, A. & Gelperin, A. Sparse odor coding in awake behaving mice. J. Neurosci. 26, 8857–8865 (2006)

  41. 41

    Huber, D. et al. Sparse optical microstimulation in barrel cortex drives learned behaviour in freely moving mice. Nature 451, 61–64 (2008)

  42. 42

    Jacobs, G. H., Neitz, J. & Deegan, J. F. Retinal receptors in rodents maximally sensitive to ultraviolet light. Nature 353, 655–656 (1991)

  43. 43

    Buzsáki, G., Leung, L. W. & Vanderwolf, C. H. Cellular bases of hippocampal EEG in the behaving rat. Brain Res. 287, 139–171 (1983)

Download references

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.

Author information

Correspondence to David W. Tank.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-12 and legends. (PDF 3729 kb)

PowerPoint slides

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.