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:

Cellular and network mechanisms of rhythmic recurrent activity in neocortex

Abstract

The neocortex generates periods of recurrent activity, such as the slow (0.1–0.5 Hz) oscillation during slow-wave sleep. Here we demonstrate that slices of ferret neocortex maintained in vitro generate this slow (< 1 Hz) rhythm when placed in a bathing medium that mimics the extracellular ionic composition in situ. This slow oscillation seems to be initiated in layer 5 as an excitatory interaction between pyramidal neurons and propagates through the neocortex. Our results demonstrate that the cerebral cortex generates an ‘up’ or depolarized state through recurrent excitation that is regulated by inhibitory networks, thereby allowing local cortical circuits to enter into temporarily activated and self-maintained excitatory states. The spontaneous generation and failure of this self-excited state may account for the generation of a subset of cortical rhythms during sleep.

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

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

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

Figure 1: Generation of the slow oscillation in vivo and in vitro.
Figure 2: The slow oscillation is generated first around layer 5 and propagates vertically.
Figure 3: The slow oscillation propagates horizontally.
Figure 4: Local application of glutamate can initiate the slow oscillation.
Figure 5: The slow oscillation can propagate through supragranular layers and depends on excitatory transmission.
Figure 6: The postsynaptic potentials underlying the depolarized state consist of both excitatory and inhibitory events.
Figure 7: The slow oscillation has a refractory period associated with hyperpolarization and decreased excitability.

Similar content being viewed by others

References

  1. Steriade, M., McCormick, D. A. & Sejnowski, T. Thalamocortical oscillations in the sleeping and aroused brain. Science 262, 679–685 (1993).

    Article  CAS  Google Scholar 

  2. Steriade, M., Nunez, A. & Amzica, F. A novel slow (&lt; 1 Hz) oscillation of neocortical neurons in vivo: depolarizing and hyperpolarizing components. J. Neurosci. 13, 3252–3265 (1993).

    Article  CAS  Google Scholar 

  3. Steriade, M., Contreras, D., Curro Dossi, R. & Nunez, A. The slow (&lt; 1 Hz) oscillation in reticular thalamic and thalamocortical neurons: scenario of sleep rhythm generation in interacting thalamic and neocortical networks. J. Neurosci. 13, 3266–3283 (1993).

    Article  CAS  Google Scholar 

  4. Steriade, M., Nunez, A. & Amzica, F. Intracellular analysis of relations between the slow (&lt; 1 Hz) neocortical oscillation and other sleep rhythms in the electroencephalogram. J. Neurosci. 13, 3266–3283 (1993).

    Article  CAS  Google Scholar 

  5. Contreras, D., Timofeev, I. & Steriade, M. Mechanisms of long-lasting hyperpolarizations underlying slow sleep oscillations in cat corticothalamic networks. J. Physiol. (Lond.) 494, 251–264 (1996).

    Article  CAS  Google Scholar 

  6. Metherate, R. & Ashe, J. H. Ionic flux contributions to neocortical slow waves and nucleus basalis-mediated activation: whole-cell recordings in vivo. J. Neurosci. 13, 5312–5323 (1993).

    Article  CAS  Google Scholar 

  7. Lampl, I., Reichova, I. & Ferster, D. Synchronous membrane potential fluctuations in neurons of the cat visual cortex. Neuron 22, 361–374 (1999).

    Article  CAS  Google Scholar 

  8. Stern, E. A., Kincaid, A. E. & Wilson, C. J. Spontaneous subthreshold membrane potential fluctuations and action potential variability of rat corticostriatal and striatal neurons in vivo. J. Neurophysiol. 77, 1697–1715 (1997).

    Article  CAS  Google Scholar 

  9. Achermann, P. & Borbely, A. A. Low-frequency (&lt; 1 Hz) oscillations in the human sleep electroencephalogram. Neuroscience 81, 213–222 (1997).

    Article  CAS  Google Scholar 

  10. von Krosigk, M., Bal, T. & McCormick, D. A. Cellular mechanisms of a synchronized oscillation in the thalamus. Science 261, 361–364 (1993).

    Article  CAS  Google Scholar 

  11. Steriade, M. & Contreras, D. Relations between cortical and thalamic cellular events during transition from sleep patterns to paroxysmal activity. J. Neurosci. 15, 623–642 (1995).

    Article  CAS  Google Scholar 

  12. Yamaguchi, T. Cerebral extracellular potassium concentration change and cerebral impedance change in short-term ischemia in gerbil. Bull. Tokyo Med. Dent. Univ. 33, 1–8 (1986).

    CAS  PubMed  Google Scholar 

  13. Zhang, E. T., Hansen, A. J., Wieloch, T. & Lauritzen, M. Influence of MK-801 on brain extracellular calcium and potassium activities in severe hypoglycemia. J. Cereb. Blood Flow Metab. 10, 136–139 (1990).

    Article  CAS  Google Scholar 

  14. Connors, B. W. Initiation of synchronized neuronal bursting in neocortex. Nature 310, 685–687 (1984).

    Article  CAS  Google Scholar 

  15. Telfeian, A. E. & Connors, B. W. Epileptiform propagation patterns mediated by NMDA and non-NMDA receptors in rat neocortex. Epilepsia 40, 1499–1506 (1999).

    Article  CAS  Google Scholar 

  16. Avoli, M., Drapeau, C., Louvel, J., Olivier, A. & Villemure, J. G. Epileptiform activity induced by low extracellular magnesium in the human cortex maintained in vitro. Ann. Neurol. 30, 589–596 (1991).

    Article  CAS  Google Scholar 

  17. Chagnac-Amitai, Y. & Connors, B. W. Horizontal spread of synchronized activity in neocortex and its control by GABA-mediated inhibition. J. Neurophysiol. 61, 747–758 (1989).

    Article  CAS  Google Scholar 

  18. McCormick, D. A., Connors, B. W., Lighthall, J. W. & Prince, D. A. Comparative electrophysiology of pyramidal and sparsely spiny neurons of the neocortex. J. Neurophysiol. 54, 782–806 (1985).

    Article  CAS  Google Scholar 

  19. Raman, I. M. & Bean, B. P. Ionic currents underlying spontaneous action potentials in isolated cerebellar Purkinje neurons. J. Neurosci. 19, 1663–1674 (1999).

    Article  CAS  Google Scholar 

  20. Haj-Dahmane, S. & Andrade, R. Ionic mechanism of the slow afterdepolarization induced by muscarinic receptor activation in rat prefrontal cortex. J. Neurophysiol. 80, 1197–1210 (1998).

    Article  CAS  Google Scholar 

  21. Wang, X.-J. Synaptic basis of cortical persistent activity: the importance of NMDA receptors to working memory. J. Neurosci. 19, 9587–9603 (1999).

    Article  CAS  Google Scholar 

  22. Nowak, L. G. & Bullier, J. in Cerebral Cortex: Extrastriate Cortex in Primates Vol. 12 (eds. Rockland, K., Kaas, J. H. & Peters, A.) 205–241 (Plenum, New York 1997).

    Book  Google Scholar 

  23. Amzica, F. & Steriade, M. Short- and long-range neuronal synchronization of the slow (&lt; 1 Hz) cortical oscillation. J. Neurophysiol. 73, 20–38 (1995).

    Article  CAS  Google Scholar 

  24. 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).

    Article  CAS  Google Scholar 

  25. Sanchez-Vives, M. V., Nowak, L. G. & McCormick, D. A. Cellular mechanisms of long lasting adaptation in visual cortical neurons in vitro. J. Neurosci. 20, 4286–4299 (2000).

    Article  CAS  Google Scholar 

  26. Schwindt, P. C., Spain, W. J. & Crill, W. E. Long-lasting reduction of excitability by a sodium-dependent potassium current in cat neocortex neurons. J. Neurophysiol. 61, 233–244 (1989).

    Article  CAS  Google Scholar 

  27. Douglas, R. J., Koch, C., Mahowald, M., Martin, K. A. & Suarez, H. H. Recurrent excitation in neocortical circuits. Science 269, 981–985 (1995).

    Article  CAS  Google Scholar 

  28. Somers, D. C., Nelson, S. B. & Sur, M. An emergent model of orientation selectivity in cat visual cortical cells. J. Neurosci. 15, 5449–5465 (1995).

    Article  Google Scholar 

  29. Staley, K. J., Longacher, M., Bains, J. S. & Yee, A. Presynaptic modulation of CA3 network activity. Nat. Neurosci. 1, 201–209 (1998).

    Article  CAS  Google Scholar 

  30. Foehring, R. C., Schwindt, P. C. & Crill, W. E. Norepinephrine selectively reduces slow Ca2+- and Na+- mediated K+ currents in cat neocortical neurons. J. Neurophysiol. 61, 245–256 (1989).

    Article  CAS  Google Scholar 

  31. Arieli, A., Sterkin, A., Grinvald, A. & Aertsen, A. Dynamics of ongoing activity: explanation of the large variability in evoked cortical responses. Science 273, 1868–1871 (1996).

    Article  CAS  Google Scholar 

  32. Steriade, M., Amzica, F. & Nunez, A. Cholinergic and noradrenergic modulation of slow (approximately 0.3 Hz) oscillation in neocortical cells. J. Neurophysiol. 70, 1385–1400 (1993).

    Article  CAS  Google Scholar 

  33. Lewandowski, M. H., Muller, C. M. & Singer, W. Reticular facilitation of cat visual cortical responses is mediated by nicotinic and muscarinic cholinergic mechanisms. Exp. Brain Res. 96, 1–7 (1993).

    Article  CAS  Google Scholar 

  34. Anderson, J., Lampl, I., Reichova, I., Carandini, M. & Ferster, D. Stimulus dependence of two-state fluctuations of membrane potential in cat visual cortex. Nat. Neurosci. 3, 617–621 (2000).

    Article  CAS  Google Scholar 

  35. Phillis, J. W. Acetylcholine release from the cerebral cortex: its role in cortical arousal. Brain Res. 7, 378–389 (1968).

    Article  CAS  Google Scholar 

  36. Luck, S. J., Chelazzi, L., Hillyard, S. A. & Desimone, R. Neural mechanisms of spatial selective attention in areas V1, V2, and V4 of macaque visual cortex. J. Neurophysiol. 77, 24–42 (1997).

    Article  CAS  Google Scholar 

  37. Mountcastle, V. B., Motter, B. C., Steinmetz, M. A. & Sestokas, A. K. Common and differential effects of attentive fixation on the excitability of parietal and prestriate (V4) cortical visual neurons in the macaque monkey. J. Neurosci. 7, 2239–2255 (1987).

    Article  CAS  Google Scholar 

  38. Goldman-Rakic, P. S. Cellular basis of working memory. Neuron 14, 477–485 (1995).

    Article  CAS  Google Scholar 

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

    Google Scholar 

  40. Lorente de No, R. Analysis of the activity of the chains of internuncial neurons. J. Neurophysiol. 1, 207–244 (1938).

    Article  Google Scholar 

  41. Snodderly, D. M. & Gur, M. Organization of striate cortex of alert, trained monkeys (Macaca fascicularis): Ongoing activity, stimulus selectivity, and widths of receptive field activating regions. J. Neurophysiol. 74, 2100–2125 (1995).

    Article  CAS  Google Scholar 

  42. Ferster, D., Chung, S. & Wheat, H. Orientation selectivity of thalamic input to simple cells of cat visual cortex. Nature 380, 249–252 (1996).

    Article  CAS  Google Scholar 

  43. Reid, R. C. & Alonso, J. M. The processing and encoding of information in the visual cortex. Curr. Opin. Neurobiol. 6, 475–480 (1996).

    Article  CAS  Google Scholar 

  44. Sanchez-Vives, M. V., Nowak, L. G. & McCormick, D. A. Membrane mechanisms underlying contrast adaptation in cat area 17 in vivo. J. Neurosci. 20, 4267–4285 (2000).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank L. G. Nowak for participation in critical portions of these experiments. We thank L. Nowak, A. Luthi, J. Brumberg, H. Blumenfeld and R. Gallego for comments on the manuscript. This work was supported by the NIH and the McKnight Foundation. For movies and additional information see http://www.mccormicklab.org.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to David A. McCormick.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sanchez-Vives, M., McCormick, D. Cellular and network mechanisms of rhythmic recurrent activity in neocortex. Nat Neurosci 3, 1027–1034 (2000). https://doi.org/10.1038/79848

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/79848

This article is cited by

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