Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Segregation of cortical head direction cell assemblies on alternating theta cycles

Nature Neuroscience volume 16, pages 739–748 (2013)Cite this article

Subjects

Abstract

High-level cortical systems for spatial navigation, including entorhinal grid cells, critically depend on input from the head direction system. We examined spiking rhythms and modes of synchrony between neurons participating in head direction networks for evidence of internal processing, independent of direct sensory drive, which may be important for grid cell function. We found that head direction networks of rats were segregated into at least two populations of neurons firing on alternate theta cycles (theta cycle skipping) with fixed synchronous or anti-synchronous relationships. Pairs of anti-synchronous theta cycle skipping neurons exhibited larger differences in head direction tuning, with a minimum difference of 40 degrees of head direction. Septal inactivation preserved the head direction signal, but eliminated theta cycle skipping of head direction cells and grid cell spatial periodicity. We propose that internal mechanisms underlying cycle skipping in head direction networks may be critical for downstream spatial computation by grid cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Theta cycle skipping covaries positively with head direction tuning.
Figure 2: Characteristics of theta cycle skipping.
Figure 3: Segregation of assemblies on alternating theta cycles.
Figure 4: Characteristics of synchronous and anti-synchronous theta cycle skipping pairs.
Figure 5: Possible downstream functional implications of theta skipping head direction cells.
Figure 6: In vitro theta cycle skipping is reduced with stronger input.
Figure 7: Stronger input can induce theta cycle skipping.

Similar content being viewed by others

References

  1. Buzsáki, G. Neural syntax: cell assemblies, synapsembles, and readers. Neuron 68, 362–385 (2010).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. Hasselmo, M.E. What is the function of hippocampal theta rhythm? Linking behavioral data to phasic properties of field potential and unit recording data. Hippocampus 15, 936–949 (2005).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  6. Kahana, M.J. et al. Human theta oscillations exhibit task dependence during virtual maze navigation. Nature 399, 781–784 (1999).

    Article  CAS  Google Scholar 

  7. Givens, B. & Olton, D.S. Bidirectional modulation of scopolamine-induced working memory impairments by muscarinic activation of the medial septal area. Neurobiol. Learn. Mem. 63, 269–276 (1995).

    Article  CAS  Google Scholar 

  8. Seager, M.A. et al. Oscillatory brain states and learning: Impact of hippocampal theta-contingent training. Proc. Natl. Acad. Sci. USA 99, 1616–1620 (2002).

    Article  CAS  Google Scholar 

  9. Givens, B.S. & Olton, D.S. Cholinergic and GABAergic modulation of the medial septal area: effect on working memory. Behav. Neurosci. 104, 849–855 (1990).

    Article  CAS  Google Scholar 

  10. Chrobak, J.J., Stackman, R.W. & Walsh, T.J. Intraseptal administration of muscimol produces dose-dependent memory impairments in the rat. Behav. Neural Biol. 52, 357–369 (1989).

    Article  CAS  Google Scholar 

  11. Klausberger, T. et al. Brain state– and cell type–specific firing of hippocampal interneurons in vivo. Nature 421, 844–848 (2003).

    Article  CAS  Google Scholar 

  12. Mizuseki, K. et al. Theta oscillations provide temporal windows for local circuit computation in the entorhinal-hippocampal loop. Neuron 64, 267–280 (2009).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Skaggs, W.E. et al. Theta phase precession in hippocampal neuronal populations and the compression of temporal sequences. Hippocampus 6, 149–172 (1996).

    Article  CAS  Google Scholar 

  15. Hafting, T. et al. Hippocampus-independent phase precession in entorhinal grid cells. Nature 453, 1248–1252 (2008).

    Article  CAS  Google Scholar 

  16. 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).

    Article  Google Scholar 

  17. Burgess, N., Barry, C. & O'Keefe, J. An oscillatory interference model of grid cell firing. Hippocampus 17, 801–812 (2007).

    Article  Google Scholar 

  18. Hasselmo, M.E., Giocomo, L.M. & Zilli, E.A. Grid cell firing may arise from interference of theta frequency membrane potential oscillations in single neurons. Hippocampus 17, 1252–1271 (2007).

    Article  Google Scholar 

  19. 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).

    Article  CAS  Google Scholar 

  20. Jensen, O. & Lisman, J.E. Novel lists of 7 ± 2 known items can be reliably stored in an oscillatory short-term memory network: interaction with long-term memory. Learn. Mem. 3, 257–263 (1996).

    Article  CAS  Google Scholar 

  21. 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).

    Article  CAS  Google Scholar 

  22. Tsodyks, M.V. et al. Population dynamics and theta rhythm phase precession of hippocampal place cell firing: a spiking neuron model. Hippocampus 6, 271–280 (1996).

    Article  CAS  Google Scholar 

  23. Burgess, N. Grid cells and theta as oscillatory interference: theory and predictions. Hippocampus 18, 1157–1174 (2008).

    Article  Google Scholar 

  24. Welday, A.C. et al. Cosine directional tuning of theta cell burst frequencies: evidence for spatial coding by oscillatory interference. J. Neurosci. 31, 16157–16176 (2011).

    Article  CAS  Google Scholar 

  25. McNaughton, B.L. et al. Path integration and the neural basis of the 'cognitive map'. Nat. Rev. Neurosci. 7, 663–678 (2006).

    Article  CAS  Google Scholar 

  26. Navratilova, Z. et al. Phase precession and variable spatial scaling in a periodic attractor map model of medial entorhinal grid cells with realistic after-spike dynamics. Hippocampus 22, 772–789 (2012).

    Article  Google Scholar 

  27. Taube, J.S. Head direction cells and the neurophysiological basis for a sense of direction. Prog. Neurobiol. 55, 225–256 (1998).

    Article  CAS  Google Scholar 

  28. Taube, J.S. Head direction cells recorded in the anterior thalamic nuclei of freely moving rats. J. Neurosci. 15, 70–86 (1995).

    Article  CAS  Google Scholar 

  29. Taube, J.S., Muller, R.U. & Ranck, J.B. Jr. Head-direction cells recorded from the postsubiculum in freely moving rats. I. Description and quantitative analysis. J. Neurosci. 10, 420–435 (1990).

    Article  CAS  Google Scholar 

  30. Cho, J. & Sharp, P.E. Head direction, place, and movement correlates for cells in the rat retrosplenial cortex. Behav. Neurosci. 115, 3–25 (2001).

    Article  CAS  Google Scholar 

  31. Boccara, C.N. et al. Grid cells in pre- and parasubiculum. Nat. Neurosci. 13, 987–994 (2010).

    Article  CAS  Google Scholar 

  32. Giocomo, L.M. et al. Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing. Science 315, 1719–1722 (2007).

    Article  CAS  Google Scholar 

  33. Sargolini, F. et al. Conjunctive representation of position, direction, and velocity in entorhinal cortex. Science 312, 758–762 (2006).

    Article  CAS  Google Scholar 

  34. Burgalossi, A. et al. Microcircuits of functionally identified neurons in the rat medial entorhinal cortex. Neuron 70, 773–786 (2011).

    Article  CAS  Google Scholar 

  35. Jeffery, K.J., Donnett, J.G. & O'Keefe, J. Medial septal control of theta-correlated unit firing in the entorhinal cortex of awake rats. Neuroreport 6, 2166–2170 (1995).

    Article  CAS  Google Scholar 

  36. Deshmukh, S.S. et al. Theta modulation in the medial and the lateral entorhinal cortices. J. Neurophysiol. 104, 994–1006 (2010).

    Article  Google Scholar 

  37. Fujisawa, S. & Buzsaki, G. A 4 Hz oscillation adaptively synchronizes prefrontal, VTA and hippocampal activities. Neuron 72, 153–165 (2011).

    Article  CAS  Google Scholar 

  38. Gevins, A. et al. High-resolution EEG mapping of cortical activation related to working memory: effects of task difficulty, type of processing and practice. Cereb. Cortex 7, 374–385 (1997).

    Article  CAS  Google Scholar 

  39. Brandon, M.P. et al. Reduction of theta rhythm dissociates grid cell spatial periodicity from directional tuning. Science 332, 595–599 (2011).

    Article  CAS  Google Scholar 

  40. Harris, K.D. et al. Organization of cell assemblies in the hippocampus. Nature 424, 552–556 (2003).

    Article  CAS  Google Scholar 

  41. Royer, S. et al. Distinct representations and theta dynamics in dorsal and ventral hippocampus. J. Neurosci. 30, 1777–1787 (2010).

    Article  CAS  Google Scholar 

  42. Brandon, M.P. et al. Head direction cells in the postsubiculum do not show replay of prior waking sequences during sleep. Hippocampus 22, 604–618 (2012).

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  45. King, C., Reece, M. & O'Keefe, J. The rhythmicity of cells of the medial septum/diagonal band of Broca in the awake freely moving rat: relationships with behaviour and hippocampal theta. Eur. J. Neurosci. 10, 464–477 (1998).

    Article  CAS  Google Scholar 

  46. Hasselmo, M.E. & Brandon, M.P. A model combining oscillations and attractor dynamics for generation of grid cell firing. Front. Neural Circuits 6, 30 (2012).

    Article  Google Scholar 

  47. Jezek, K. et al. Theta-paced flickering between place-cell maps in the hippocampus. Nature 478, 246–249 (2011).

    Article  CAS  Google Scholar 

  48. Colgin, L.L. et al. Frequency of gamma oscillations routes flow of information in the hippocampus. Nature 462, 353–357 (2009).

    Article  CAS  Google Scholar 

  49. Lisman, J. & Buzsaki, G. A neural coding scheme formed by the combined function of gamma and theta oscillations. Schizophr. Bull. 34, 974–980 (2008).

    Article  Google Scholar 

  50. Howard, M.W. et al. Gamma oscillations correlate with working memory load in humans. Cereb. Cortex 13, 1369–1374 (2003).

    Article  Google Scholar 

  51. Taube, J.S., Muller, R.U. & Ranck, J.B. Jr. Head-direction cells recorded from the postsubiculum in freely moving rats. II. Effects of environmental manipulations. J. Neurosci. 10, 436–447 (1990).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We kindly thank S. Gillet, J. Hinman, E. Newman and L. Ewell for their invaluable consultations and comments on previous versions of this manuscript, as well as M. Connerney, S. Eriksson, C. Libby and T. Ware for technical assistance and behavioral training. This work was supported by grants from the National Institute of Mental Health (R01 MH60013 and MH61492) and the Office of Naval Research Multidisciplinary University Research Initiative (N00014-10-1-0936).

Author information

Author notes

  1. Mark P Brandon & Andrew R Bogaard

    Present address: Present address: Medical Scientist Training Program, University of Washington, Seattle, Washington, USA (A.R.B.), and Center for Neural Circuits and Behavior, Neurobiology Section, Division of Biological Sciences, University of California, San Diego, California, USA (M.P.B.).,

  2. Mark P Brandon and Andrew R Bogaard: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Psychology, Center for Memory and Brain, Graduate Program for Neuroscience, Boston University, Boston, Massachusetts, USA

    Mark P Brandon, Andrew R Bogaard, Nathan W Schultheiss & Michael E Hasselmo

Authors
  1. Mark P Brandon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andrew R Bogaard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nathan W Schultheiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michael E Hasselmo
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.P.B. and M.E.H. designed the in vivo experiments. M.P.B. collected the in vivo data. M.P.B., A.R.B. and N.W.S. designed, and A.R.B. implemented, the in vivo analyses. N.W.S. and M.E.H. designed the in vitro experiments. N.W.S. collected and analyzed the in vitro data. M.E.H. created the network simulations and A.R.B. developed the Poisson model. M.P.B., A.R.B., N.W.S. and M.E.H. wrote the manuscript.

Corresponding author

Correspondence to Mark P Brandon.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6 and Supplementary Modeling (PDF 1620 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Brandon, M., Bogaard, A., Schultheiss, N. et al. Segregation of cortical head direction cell assemblies on alternating theta cycles. Nat Neurosci 16, 739–748 (2013). https://doi.org/10.1038/nn.3383

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nn.3383

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing