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.

  • Opinion
  • Published:

Neural signatures of cell assembly organization

Nature Reviews Neuroscience volume 6, pages 399–407 (2005)Cite this article

Abstract

Cortical neurons show irregular but structured spike trains. This has been interpreted as evidence for 'temporal coding', whereby stimuli are represented by precise spike-timing patterns. Here, we suggest an alternative interpretation based on the older concept of the cell assembly. The dynamic evolution of assembly sequences, which are steered but not deterministically controlled by sensory input, is the proposed substrate of psychological processes beyond simple stimulus–response associations. Accordingly, spike trains show a temporal structure that is stimulus-dependent and more variable than would be predicted by strict sensory control. We propose four signatures of assembly organization that can be experimentally tested. We argue that many observations that have been interpreted as evidence for temporal coding might instead reflect an underlying assembly structure.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1: The cell assembly hypothesis.
Figure 2: Assembly structure analysis.
Figure 3: Spike timing of hippocampal neurons.
Figure 4: Peer prediction analysis of assembly organization in the hippocampus.
Figure 5: Stimulus reconstruction and peer prediction paradigms.
Figure 6: Timescales of synchronization.

Similar content being viewed by others

References

  1. deCharms, R. C. & Zador, A. Neural representation and the cortical code. Annu. Rev. Neurosci. 23, 613–647 (2000).

    CAS  PubMed  Google Scholar 

  2. Theunissen, F. & Miller, J. P. Temporal encoding in nervous systems: a rigorous definition. J. Comput. Neurosci. 2, 149–162 (1995).

    CAS  PubMed  Google Scholar 

  3. Gerstner, W. Pulsed Neural Networks (eds Maas, W. & Bishop, C. M.) 3–49 (MIT Press, Cambridge, Massachusetts, 1999).

    Google Scholar 

  4. Magee, J. C. Dendritic integration of excitatory synaptic input. Nature Rev. Neurosci. 1, 181–190 (2000).

    Article  CAS  Google Scholar 

  5. Abeles, M. Role of the cortical neuron: integrator or coincidence detector? Isr. J. Med. Sci. 18, 83–92 (1982).

    CAS  PubMed  Google Scholar 

  6. Konig, P., Engel, A. K. & Singer, W. Integrator or coincidence detector? The role of the cortical neuron revisited. Trends Neurosci. 19, 130–137 (1996).

    CAS  PubMed  Google Scholar 

  7. Spruston, N. & Johnston, D. Perforated patch-clamp analysis of the passive membrane properties of three classes of hippocampal neurons. J. Neurophysiol. 67, 508–529 (1992).

    CAS  PubMed  Google Scholar 

  8. Zhang, Z. W. Maturation of layer V pyramidal neurons in the rat prefrontal cortex: intrinsic properties and synaptic function. J. Neurophysiol. 91, 1171–1182 (2004).

    PubMed  Google Scholar 

  9. Leger, J. F., Stern, E. A., Aertsen, A. & Heck, D. Synaptic integration in rat frontal cortex shaped by network activity. J. Neurophysiol. 93, 281–293 (2005).

    PubMed  Google Scholar 

  10. Trevelyan, A. J. & Jack, J. Detailed passive cable models of layer 2/3 pyramidal cells in rat visual cortex at different temperatures. J. Physiol. (Lond.) 539, 623–636 (2002).

    CAS  Google Scholar 

  11. Koch, C., Rapp, M. & Segev, I. A brief history of time (constants). Cereb. Cortex 6, 93–101 (1996).

    CAS  PubMed  Google Scholar 

  12. Destexhe, A. & Pare, D. Impact of network activity on the integrative properties of neocortical pyramidal neurons in vivo. J. Neurophysiol. 81, 1531–1547 (1999).

    CAS  PubMed  Google Scholar 

  13. Zhou, Y. D. & Fuster, J. M. Visuo-tactile cross-modal associations in cortical somatosensory cells. Proc. Natl Acad. Sci. USA 97, 9777–9782 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Kreiman, G., Koch, C. & Fried, I. Imagery neurons in the human brain. Nature 408, 357–361 (2000).

    CAS  PubMed  Google Scholar 

  15. Kosslyn, S. M., Thompson, W. L., Kim, I. J. & Alpert, N. M. Topographical representations of mental images in primary visual cortex. Nature 378, 496–498 (1995).

    CAS  PubMed  Google Scholar 

  16. Sakurai, Y. Involvement of auditory cortical and hippocampal neurons in auditory working memory and reference memory in the rat. J. Neurosci. 14, 2606–2623 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Tsodyks, M., Kenet, T., Grinvald, A. & Arieli, A. Linking spontaneous activity of single cortical neurons and the underlying functional architecture. Science 286, 1943–1946 (1999).

    CAS  PubMed  Google Scholar 

  18. Kenet, T., Bibitchkov, D., Tsodyks, M., Grinvald, A. & Arieli, A. Spontaneously emerging cortical representations of visual attributes. Nature 425, 954–956 (2003).

    CAS  PubMed  Google Scholar 

  19. Fiser, J., Chiu, C. & Weliky, M. Small modulation of ongoing cortical dynamics by sensory input during natural vision. Nature 431, 573–578 (2004).

    CAS  PubMed  Google Scholar 

  20. Llinas, R. R. & Pare, D. Of dreaming and wakefulness. Neuroscience 44, 521–535 (1991).

    CAS  PubMed  Google Scholar 

  21. Hebb, D. O. The Organization of Behavior (Wiley, New York, 1949).

    Google Scholar 

  22. Tolman, E. C. Purposive Behavior in Animals and Men (Appleton–Century–Crofts, New York, 1932).

    Google Scholar 

  23. Skinner, B. F. The Behavior of Organisms: an Experimental Analysis (Appleton–Century–Crofts, New York, 1938).

    Google Scholar 

  24. Gabbiani, F., Metzner, W., Wessel, R. & Koch, C. From stimulus encoding to feature extraction in weakly electric fish. Nature 384, 564–567 (1996).

    CAS  PubMed  Google Scholar 

  25. Buracas, G. T., Zador, A. M., DeWeese, M. R. & Albright, T. D. Efficient discrimination of temporal patterns by motion-sensitive neurons in primate visual cortex. Neuron 20, 959–969 (1998).

    CAS  PubMed  Google Scholar 

  26. Optican, L. M. & Richmond, B. J. Temporal encoding of two-dimensional patterns by single units in primate inferior temporal cortex. III. Information theoretic analysis. J. Neurophysiol. 57, 162–178 (1987).

    CAS  PubMed  Google Scholar 

  27. Hegde, J. & Van Essen, D. C. Temporal dynamics of shape analysis in macaque visual area V2. J. Neurophysiol. 92, 3030–3042 (2004).

    PubMed  Google Scholar 

  28. Middlebrooks, J. C., Clock, A. E., Xu, L. & Green, D. M. A panoramic code for sound location by cortical neurons. Science 264, 842–844 (1994).

    CAS  PubMed  Google Scholar 

  29. Panzeri, S., Petersen, R. S., Schultz, S. R., Lebedev, M. & Diamond, M. E. The role of spike timing in the coding of stimulus location in rat somatosensory cortex. Neuron 29, 769–777 (2001).

    CAS  PubMed  Google Scholar 

  30. Katz, D. B., Simon, S. A. & Nicolelis, M. A. Dynamic and multimodal responses of gustatory cortical neurons in awake rats. J. Neurosci. 21, 4478–4489 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Di Lorenzo, P. M. & Victor, J. D. Taste response variability and temporal coding in the nucleus of the solitary tract of the rat. J. Neurophysiol. 90, 1418–1431 (2003).

    PubMed  Google Scholar 

  32. Laurent, G. Dynamical representation of odors by oscillating and evolving neural assemblies. Trends Neurosci. 19, 489–496 (1996).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  34. 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  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  36. 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).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Stopfer, M., Jayaraman, V. & Laurent, G. Intensity versus identity coding in an olfactory system. Neuron 39, 991–1004 (2003).

    CAS  PubMed  Google Scholar 

  39. MacLeod, K., Backer, A. & Laurent, G. Who reads temporal information contained across synchronized and oscillatory spike trains? Nature 395, 693–698 (1998).

    CAS  PubMed  Google Scholar 

  40. Stopfer, M., Bhagavan, S., Smith, B. H. & Laurent, G. Impaired odour discrimination on desynchronization of odour-encoding neural assemblies. Nature 390, 70–74 (1997).

    CAS  PubMed  Google Scholar 

  41. Perez-Orive, J., Bazhenov, M. & Laurent, G. Intrinsic and circuit properties favor coincidence detection for decoding oscillatory input. J. Neurosci. 24, 6037–6047 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Adrian, E. D. & Zotterman, Y. The impulses produced by sensory nerve endings. Part 2. The response of a single end organ. J. Physiol. (Lond.) 61, 151–171 (1926).

    CAS  Google Scholar 

  43. Britten, K. H., Shadlen, M. N., Newsome, W. T. & Movshon, J. A. Responses of neurons in macaque MT to stochastic motion signals. Vis. Neurosci. 10, 1157–1169 (1993).

    CAS  PubMed  Google Scholar 

  44. Softky, W. R. & Koch, C. The highly irregular firing of cortical cells is inconsistent with temporal integration of random EPSPs. J. Neurosci. 13, 334–350 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Shadlen, M. N. & Newsome, W. T. The variable discharge of cortical neurons: implications for connectivity, computation, and information coding. J. Neurosci. 18, 3870–3896 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Mazurek, M. E. & Shadlen, M. N. Limits to the temporal fidelity of cortical spike rate signals. Nature Neurosci. 5, 463–471 (2002).

    CAS  PubMed  Google Scholar 

  47. Stevens, C. F. & Zador, A. M. Input synchrony and the irregular firing of cortical neurons. Nature Neurosci. 1, 210–217 (1998).

    CAS  PubMed  Google Scholar 

  48. Bair, W., Zohary, E. & Newsome, W. T. Correlated firing in macaque visual area MT: time scales and relationship to behavior. J. Neurosci. 21, 1676–1697 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Teich, M. C. Fractal character of the auditory neural spike train. IEEE Trans. Biomed. Eng. 36, 150–160 (1989).

    CAS  PubMed  Google Scholar 

  50. Baddeley, R. et al. Responses of neurons in primary and inferior temporal visual cortices to natural scenes. Proc. R. Soc. Lond. B 264, 1775–1783 (1997).

    CAS  Google Scholar 

  51. Kara, P., Reinagel, P. & Reid, R. C. Low response variability in simultaneously recorded retinal, thalamic, and cortical neurons. Neuron 27, 635–646 (2000).

    CAS  PubMed  Google Scholar 

  52. DeWeese, M. R. & Zador, A. M. Shared and private variability in the auditory cortex. J. Neurophysiol. (2004).

  53. Wehr, M. & Zador, A. M. Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex. Nature 426, 442–446 (2003).

    CAS  PubMed  Google Scholar 

  54. DeWeese, M. R., Wehr, M. & Zador, A. M. Binary spiking in auditory cortex. J. Neurosci. 23, 7940–7949 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Fenton, A. A. & Muller, R. U. Place cell discharge is extremely variable during individual passes of the rat through the firing field. Proc. Natl Acad. Sci. USA 95, 3182–3187 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Mainen, Z. F. & Sejnowski, T. J. Reliability of spike timing in neocortical neurons. Science 268, 1503–1506 (1995).

    CAS  PubMed  Google Scholar 

  57. Fellous, J. M., Tiesinga, P. H., Thomas, P. J. & Sejnowski, T. J. Discovering spike patterns in neuronal responses. J. Neurosci. 24, 2989–3001 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Gerstein, G. L. & Mandelbrot, B. Random walk models for the spike activity of a single neuron. Biophys. J. 71, 41–68 (1964).

    Google Scholar 

  59. Chance, F. S., Abbott, L. F. & Reyes, A. D. Gain modulation from background synaptic input. Neuron 35, 773–782 (2002).

    CAS  PubMed  Google Scholar 

  60. Berry, M. J., Warland, D. K. & Meister, M. The structure and precision of retinal spike trains. Proc. Natl Acad. Sci. USA 94, 5411–5416 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Bair, W. & Koch, C. Temporal precision of spike trains in extrastriate cortex of the behaving macaque monkey. Neural Comput. 8, 1185–1202 (1996).

    CAS  PubMed  Google Scholar 

  62. Harris, K. D., Csicsvari, J., Hirase, H., Dragoi, G. & Buzsaki, G. Organization of cell assemblies in the hippocampus. Nature 424, 552–556 (2003).

    CAS  PubMed  Google Scholar 

  63. Wood, E. R., Dudchenko, P. A., Robitsek, R. J. & Eichenbaum, H. Hippocampal neurons encode information about different types of memory episodes occurring in the same location. Neuron 27, 623–633 (2000).

    CAS  PubMed  Google Scholar 

  64. Oram, M. W., Foldiak, P., Perrett, D. I. & Sengpiel, F. The 'ideal homunculus': decoding neural population signals. Trends Neurosci. 21, 259–265 (1998).

    CAS  PubMed  Google Scholar 

  65. Ghazanfar, A. A., Stambaugh, C. R. & Nicolelis, M. A. Encoding of tactile stimulus location by somatosensory thalamocortical ensembles. J. Neurosci. 20, 3761–3775 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Furukawa, S., Xu, L. & Middlebrooks, J. C. Coding of sound-source location by ensembles of cortical neurons. J. Neurosci. 20, 1216–1228 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Oram, M. W., Hatsopoulos, N. G., Richmond, B. J. & Donoghue, J. P. Excess synchrony in motor cortical neurons provides redundant direction information with that from coarse temporal measures. J. Neurophysiol. 86, 1700–1716 (2001).

    CAS  PubMed  Google Scholar 

  68. Engel, A. K., Fries, P. & Singer, W. Dynamic predictions: oscillations and synchrony in top-down processing. Nature Rev. Neurosci. 2, 704–716 (2001).

    CAS  Google Scholar 

  69. Riehle, A., Grun, S., Diesmann, M. & Aertsen, A. Spike synchronization and rate modulation differentially involved in motor cortical function. Science 278, 1950–1953 (1997).

    CAS  PubMed  Google Scholar 

  70. Fries, P., Reynolds, J. H., Rorie, A. E. & Desimone, R. Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291, 1560–1563 (2001).

    CAS  PubMed  Google Scholar 

  71. von Stein, A., Chiang, C. & Konig, P. Top–down processing mediated by interareal synchronization. Proc. Natl Acad. Sci. USA 97, 14748–14753 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. Gray, C. M., Konig, P., Engel, A. K. & Singer, W. Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties. Nature 338, 334–337 (1989).

    CAS  PubMed  Google Scholar 

  73. Wilson, M. A. & McNaughton, B. L. Reactivation of hippocampal ensemble memories during sleep. Science 265, 676–679 (1994).

    CAS  PubMed  Google Scholar 

  74. Louie, K. & Wilson, M. A. Temporally structured replay of awake hippocampal ensemble activity during rapid eye movement sleep. Neuron 29, 145–156 (2001).

    CAS  PubMed  Google Scholar 

  75. Skaggs, W. E. & McNaughton, B. L. Replay of neuronal firing sequences in rat hippocampus during sleep following spatial experience. Science 271, 1870–1873 (1996).

    CAS  PubMed  Google Scholar 

  76. Lee, A. K. & Wilson, M. A. Memory of sequential experience in the hippocampus during slow wave sleep. Neuron 36, 1183–1194 (2002).

    CAS  PubMed  Google Scholar 

  77. Nadasdy, Z., Hirase, H., Czurko, A., Csicsvari, J. & Buzsaki, G. Replay and time compression of recurring spike sequences in the hippocampus. J. Neurosci. 19, 9497–9507 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  78. Kudrimoti, H. S., Barnes, C. A. & McNaughton, B. L. Reactivation of hippocampal cell assemblies: effects of behavioral state, experience, and EEG dynamics. J. Neurosci. 19, 4090–4101 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  79. Hoffman, K. L. & McNaughton, B. L. Coordinated reactivation of distributed memory traces in primate neocortex. Science 297, 2070–2073 (2002).

    CAS  PubMed  Google Scholar 

  80. Hirase, H., Leinekugel, X., Czurko, A., Csicsvari, J. & Buzsaki, G. Firing rates of hippocampal neurons are preserved during subsequent sleep episodes and modified by novel awake experience. Proc. Natl Acad. Sci. USA 98, 9386–9390 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  81. Usrey, W. M. & Reid, R. C. Synchronous activity in the visual system. Annu. Rev. Physiol. 61, 435–456 (1999).

    CAS  PubMed  Google Scholar 

  82. Constantinidis, C., Franowicz, M. N. & Goldman-Rakic, P. S. Coding specificity in cortical microcircuits: a multiple-electrode analysis of primate prefrontal cortex. J. Neurosci. 21, 3646–3655 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Csicsvari, J., Hirase, H., Czurko, A. & Buzsaki, G. Reliability and state dependence of pyramidal cell-interneuron synapses in the hippocampus: an ensemble approach in the behaving rat. Neuron 21, 179–189 (1998).

    CAS  PubMed  Google Scholar 

  84. deCharms, R. C. & Merzenich, M. M. Primary cortical representation of sounds by the coordination of action-potential timing. Nature 381, 610–613 (1996).

    CAS  PubMed  Google Scholar 

  85. Vaadia, E. et al. Dynamics of neuronal interactions in monkey cortex in relation to behavioural events. Nature 373, 515–518 (1995).

    CAS  PubMed  Google Scholar 

  86. Bartho, P. et al. Characterization of neocortical principal cells and interneurons by network interactions and extracellular features. J. Neurophysiol. 92, 600–608 (2004).

    PubMed  Google Scholar 

  87. Marshall, L. et al. Hippocampal pyramidal cell-interneuron spike transmission is frequency dependent and responsible for place modulation of interneuron discharge. J. Neurosci. 22, RC197 (2002).

    PubMed  PubMed Central  Google Scholar 

  88. Csicsvari, J., Jamieson, B., Wise, K. D. & Buzsaki, G. Mechanisms of gamma oscillations in the hippocampus of the behaving rat. Neuron 37, 311–322 (2003).

    CAS  PubMed  Google Scholar 

  89. Bi, G. Q. & Poo, M. -M. Synaptic modifications in cultured hippocampal neurons: dependence on spike timing, synaptic strength, and postsynaptic cell type. J. Neurosci. 18, 10464–10472 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  90. Magee, J. C. & Johnston, D. A synaptically controlled, associative signal for Hebbian plasticity in hippocampal neurons. Science 275, 209–213 (1997).

    CAS  PubMed  Google Scholar 

  91. Singer, W. Synchronization of cortical activity and its putative role in information processing and learning. Annu. Rev. Physiol. 55, 349–374 (1993).

    CAS  PubMed  Google Scholar 

  92. Marr, D. Simple memory: a theory for archicortex. Philos. Trans. R. Soc. Lond. B 262, 23–81 (1971).

    CAS  Google Scholar 

  93. Gardner-Medwin, A. R. The recall of events through the learning of associations between their parts. Proc. R. Soc. Lond. B 194, 375–402 (1976).

    CAS  PubMed  Google Scholar 

  94. Hopfield, J. J. Neural networks and physical systems with emergent collective computational abilities. Proc. Natl Acad. Sci. USA 79, 2554–2558 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Amit, D. The Hebbian paradigm reintegrated: local reverberations as internal representations. Behav. Brain Sci. 18, 617–626 (1994).

    Google Scholar 

  96. 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).

    CAS  PubMed  Google Scholar 

  97. Izhikevich, E. M., Gally, J. A. & Edelman, G. M. Spike-timing dynamics of neuronal groups. Cereb. Cortex 14, 933–944 (2004).

    PubMed  Google Scholar 

  98. Barlow, H. B. Single units and sensation: a neuron doctrine for perceptual psychology? Perception 1, 371–394 (1972).

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I thank G. Buzsaki, S. Montgomery and E. Ludvig for comments on the manuscript. K.D.H. is supported by NIH and an Alfred P. Sloan research fellowship.

Author information

Authors and Affiliations

  1. the Center for Molecular and Behavioral Neuroscience, Rutgers, The State University of New Jersey, 197 University Avenue, Newark, 07102, New Jersey, USA

    Kenneth D. Harris

Authors
  1. Kenneth D. Harris
    View author publications

    You can also search for this author in PubMed Google Scholar

Ethics declarations

Competing interests

The author declares no competing financial interests.

Related links

Related links

FURTHER INFORMATION

Kenneth Harris's homepage

Rights and permissions

Reprints and permissions

About this article

Cite this article

Harris, K. Neural signatures of cell assembly organization. Nat Rev Neurosci 6, 399–407 (2005). https://doi.org/10.1038/nrn1669

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn1669

This article is cited by

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