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Hippocampal theta oscillations are travelling waves

Abstract

Theta oscillations clock hippocampal activity during awake behaviour and rapid eye movement (REM) sleep. These oscillations are prominent in the local field potential, and they also reflect the subthreshold membrane potential and strongly modulate the spiking of hippocampal neurons. The prevailing view is that theta oscillations are synchronized throughout the hippocampus, despite the lack of conclusive experimental evidence. In contrast, here we show that in freely behaving rats, theta oscillations in area CA1 are travelling waves that propagate roughly along the septotemporal axis of the hippocampus. Furthermore, we find that spiking in the CA1 pyramidal cell layer is modulated in a consistent travelling wave pattern. Our results demonstrate that theta oscillations pattern hippocampal activity not only in time, but also across anatomical space. The presence of travelling waves indicates that the instantaneous output of the hippocampus is topographically organized and represents a segment, rather than a point, of physical space.

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Figure 1: Interlaminar depth profile of theta oscillations and ripples.
Figure 2: Example of theta phase deviations.
Figure 3: Topographic intralaminar theta phase profiles.
Figure 4: Travelling wave example and wave parameter distributions.
Figure 5: Topographic profile of spiking theta phase preference.
Figure 6: Hippocampal representation of physical space.

References

  1. 1

    Green, J. D. & Arduini, A. A. Hippocampal electrical activity in arousal. J. Neurophysiol. 17, 533–557 (1954)

    CAS  Article  Google Scholar 

  2. 2

    Vanderwolf, C. H. Hippocampal electrical activity and voluntary movement in the rat. Electroencephalogr. Clin. Neurophysiol. 26, 407–418 (1969)

    CAS  Article  Google Scholar 

  3. 3

    Winson, J. Interspecies differences in the occurrence of theta. Behav. Biol. 7, 479–487 (1972)

    CAS  Article  Google Scholar 

  4. 4

    Arnolds, D. E., Lopes da Silva, F. H., Aitink, J. W., Kamp, A. & Boeijinga, P. The spectral properties of hippocampal EEG related to behaviour in man. Electroencephalogr. Clin. Neurophysiol. 50, 324–328 (1980)

    CAS  Article  Google Scholar 

  5. 5

    O’Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Oxford Univ. Press, 1978)

    Google Scholar 

  6. 6

    Winson, J. Loss of hippocampal theta rhythm results in spatial memory deficit in the rat. Science 201, 160–163 (1978)

    ADS  CAS  Article  Google Scholar 

  7. 7

    Mitchell, S. J., Rawlins, J. N., Steward, O. & Olton, D. S. Medial septal area lesions disrupt theta rhythm and cholinergic staining in medial entorhinal cortex and produce impaired radial arm maze behavior in rats. J. Neurosci. 2, 292–302 (1982)

    CAS  Article  Google Scholar 

  8. 8

    Fujita, Y. & Sato, T. Intracellular records from hippocampal pyramidal cells in rabbit during theta rhythm activity. J. Neurophysiol. 27, 1012–1025 (1964)

    Article  Google Scholar 

  9. 9

    Leung, L. S. & Yim, C. Y. Intracellular records of theta rhythm in hippocampal CA1 cells of the rat. Brain Res. 367, 323–327 (1986)

    CAS  Article  Google Scholar 

  10. 10

    Vertes, R. P. & Kocsis, B. Brainstem-diencephalo-septohippocampal systems controlling the theta rhythm of the hippocampus. Neuroscience 81, 893–926 (1997)

    CAS  Article  Google Scholar 

  11. 11

    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)

    Article  Google Scholar 

  12. 12

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

    CAS  Article  Google Scholar 

  13. 13

    Fox, S. E., Wolfson, S. & Ranck, J. B. Hippocampal theta rhythm and the firing of neurons in walking and urethane anesthetized rats. Exp. Brain Res. 62, 495–508 (1986)

    CAS  Article  Google Scholar 

  14. 14

    Pavlides, C., Greenstein, Y. J., Grudman, M. & Winson, J. Long-term potentiation in the dentate gyrus is induced preferentially on the positive phase of theta-rhythm. Brain Res. 439, 383–387 (1988)

    CAS  Article  Google Scholar 

  15. 15

    Huerta, P. T. & Lisman, J. E. Heightened synaptic plasticity of hippocampal CA1 neurons during a cholinergically induced rhythmic state. Nature 364, 723–725 (1993)

    ADS  CAS  Article  Google Scholar 

  16. 16

    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)

    Article  Google Scholar 

  17. 17

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

    Article  Google Scholar 

  18. 18

    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)

    CAS  Article  Google Scholar 

  19. 19

    Huxter, J., Burgess, N. & O’Keefe, J. Independent rate and temporal coding in hippocampal pyramidal cells. Nature 425, 828–832 (2003)

    ADS  CAS  Article  Google Scholar 

  20. 20

    Debanne, D., Gahwiler, B. H. & Thompson, S. M. Long-term synaptic plasticity between pairs of individual CA3 pyramidal cells in rat hippocampal slice cultures. J. Physiol. (Lond.) 507, 237–247 (1998)

    CAS  Article  Google Scholar 

  21. 21

    Lisman, J. E. Relating hippocampal circuitry to function: recall of memory sequences by reciprocal dentate-CA3 interactions. Neuron 22, 233–242 (1999)

    CAS  Article  Google Scholar 

  22. 22

    Pedemonte, M., Pena, J. L. & Velluti, R. A. Firing of inferior colliculus auditory neurons is phase-locked to the hippocampus theta rhythm during paradoxical sleep and waking. Exp. Brain Res. 112, 41–46 (1996)

    CAS  Article  Google Scholar 

  23. 23

    Alonso, A. & Garcia-Austt, E. Neuronal sources of theta rhythm in the entorhinal cortex of the rat. II. Phase relations between unit discharges and theta field potentials. Exp. Brain Res. 67, 502–509 (1987)

    CAS  Article  Google Scholar 

  24. 24

    Siapas, A. G., Lubenov, E. V. & Wilson, M. A. Prefrontal phase locking to hippocampal theta oscillations. Neuron 46, 141–151 (2005)

    CAS  Article  Google Scholar 

  25. 25

    Green, J. D., Maxwell, D. S., Schindler, W. J. & Stumpf, C. Rabbit EEG ‘theta’ rhythm: its anatomical source and relation to activity in single neurons. J. Neurophysiol. 23, 403–420 (1960)

    Article  Google Scholar 

  26. 26

    Petsche, H. & Stumpf, C. Topographic and toposcopic study of origin and spread of the regular synchronized arousal pattern in the rabbit. Electroencephalogr. Clin. Neurophysiol. 12, 589–600 (1960)

    CAS  Article  Google Scholar 

  27. 27

    Winson, J. Patterns of hippocampal theta rhythm in the freely moving rat. Electroencephalogr. Clin. Neurophysiol. 36, 291–301 (1974)

    CAS  Article  Google Scholar 

  28. 28

    Bland, B. H., Anderson, P. & Ganes, T. Two generators of hippocampal theta activity in rabbits. Brain Res. 94, 199–218 (1975)

    CAS  Article  Google Scholar 

  29. 29

    Leung, L. W. Model of gradual phase shift of theta rhythm in the rat. J. Neurophysiol. 52, 1051–1065 (1984)

    CAS  Article  Google Scholar 

  30. 30

    Buzsaki, G., Czopf, J., Kondakor, I. & Kellenyi, L. Laminar distribution of hippocampal rhythmic slow activity (RSA) in the behaving rat: current-source density analysis, effects of urethane and atropine. Brain Res. 365, 125–137 (1986)

    CAS  Article  Google Scholar 

  31. 31

    Kocsis, B., Bragin, A. & Buzsaki, G. Interdependence of multiple theta generators in the hippocampus: a partial coherence analysis. J. Neurosci. 19, 6200–6212 (1999)

    CAS  Article  Google Scholar 

  32. 32

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

    CAS  Article  Google Scholar 

  33. 33

    Bullock, T. H., Buzsaki, G. & McClune, M. C. Coherence of compound field potentials reveals discontinuities in the CA1-subiculum of the hippocampus in freely-moving rats. Neuroscience 38, 609–619 (1990)

    CAS  Article  Google Scholar 

  34. 34

    Bragin, A. et al. Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J. Neurosci. 15, 47–60 (1995)

    CAS  Article  Google Scholar 

  35. 35

    Amaral, D. G. & Witter, M. P. in The Rat Nervous System (ed. Paxinos G.) Ch. 21, 443–493 (Academic, 2004)

    Google Scholar 

  36. 36

    van Groen, T. & Wyss, J. M. Extrinsic projections from area CA1 of the rat hippocampus: olfactory, cortical, subcortical, and bilateral hippocampal formation projections. J. Comp. Neurol. 302, 515–528 (1990)

    CAS  Article  Google Scholar 

  37. 37

    Cenquizca, L. A. & Swanson, L. W. Spatial organization of direct hippocampal field CA1 axonal projections to the rest of the cerebral cortex. Brain Res. Rev. 56, 1–26 (2007)

    CAS  Article  Google Scholar 

  38. 38

    Jung, M. W., Wiener, S. I. & McNaughton, B. L. Comparison of spatial firing characteristics of units in dorsal and ventral hippocampus of the rat. J. Neurosci. 14, 7347–7356 (1994)

    CAS  Article  Google Scholar 

  39. 39

    Maurer, A. P., Vanrhoads, S. R., Sutherland, G. R., Lipa, P. & McNaughton, B. L. Self-motion and the origin of differential spatial scaling along the septo-temporal axis of the hippocampus. Hippocampus 15, 841–852 (2005)

    Article  Google Scholar 

  40. 40

    Kjelstrup, K. B. et al. Finite scale of spatial representation in the hippocampus. Science 321, 140–143 (2008)

    ADS  CAS  Article  Google Scholar 

  41. 41

    Huxter, J. R., Senior, T. J., Allen, K. & Csicsvari, J. Theta phase-specific codes for two-dimensional position, trajectory and heading in the hippocampus. Nature Neurosci. 11, 587–594 (2008)

    CAS  Article  Google Scholar 

  42. 42

    Ermentrout, G. B. & Kleinfeld, D. Traveling electrical waves in cortex: insights from phase dynamics and speculation on a computational role. Neuron 29, 33–44 (2001)

    CAS  Article  Google Scholar 

  43. 43

    Miles, R., Traub, R. D. & Wong, R. K. Spread of synchronous firing in longitudinal slices from the CA3 region of the hippocampus. J. Neurophysiol. 60, 1481–1496 (1988)

    CAS  Article  Google Scholar 

  44. 44

    Traub, R. D. & Miles, R. Neuronal Networks of the Hippocampus Ch. 6, 119–156 (Cambridge Univ. Press, 1991)

    Book  Google Scholar 

  45. 45

    Alonso, A. & Llinas, R. R. Subthreshold Na+-dependent theta-like rhythmicity in stellate cells of entorhinal cortex layer II. Nature 342, 175–177 (1989)

    ADS  CAS  Article  Google Scholar 

  46. 46

    Haas, J. S. & White, J. A. Frequency selectivity of layer II stellate cells in the medial entorhinal cortex. J. Neurophysiol. 88, 2422–2429 (2002)

    Article  Google Scholar 

  47. 47

    Giocomo, L. M., Zilli, E. A., Fransen, E. & Hasselmo, M. E. Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing. Science 315, 1719–1722 (2007)

    ADS  CAS  Article  Google Scholar 

  48. 48

    Leung, L. S. & Yu, H.-W. Theta-frequency resonance in hippocampal CA1 neurons in vitro demonstrated by sinusoidal current injection. J. Neurophysiol. 79, 1592–1596 (1998)

    CAS  Article  Google Scholar 

  49. 49

    Cobb, S. R., Buhl, E. H., Halasy, K., Paulsen, O. & Somogyi, P. Synchronization of neuronal activity in hippocampus by individual GABAergic interneurons. Nature 378, 75–78 (1995)

    ADS  CAS  Article  Google Scholar 

  50. 50

    Miller, R. Cortico-Hippocampal Interplay and the Representation of Contexts in the Brain Ch. 9, 159–188 (Springer-Verlag, 1991)

    Google Scholar 

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Acknowledgements

We thank C. Wierzynski, M. Gu, G. Laurent, E. Schuman and A. Tolias for critical discussions and comments on the manuscript. We also thank the Caltech Brain Imaging Center and D. Procissi for the MRI brain scans. This work was supported by the Caltech Information Science and Technology Center for Biological Circuit Design, a 21st Century McDonnell Foundation Award, the Bren Foundation, and the McKnight Foundation.

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Correspondence to Evgueniy V. Lubenov or Athanassios G. Siapas.

Supplementary information

Supplementary Information

This file contains Supplementary Methods and Data, Supplementary Notes for Supplementary Movies 1-3, Supplementary References and Supplementary Figures S1-S27 with Legends. (PDF 13325 kb)

Supplementary Movie 1

This movie shows travelling theta wave in rat 1 implanted with 6x5 grid (see file S1 for full Notes). (MOV 748 kb)

Supplementary Movie 2

This movie shows travelling theta wave in rat 2 implanted with 4x8 grid (see file S1 for full Notes). (MOV 730 kb)

Supplementary Movie 3

This movie shows travelling theta wave in rat 3 implanted with 5x6 grid (see file S1 for full Notes). (MOV 787 kb)

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Lubenov, E., Siapas, A. Hippocampal theta oscillations are travelling waves. Nature 459, 534–539 (2009). https://doi.org/10.1038/nature08010

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