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.

  • Letter
  • Published:

Rapid developmental switch in the mechanisms driving early cortical columnar networks

Abstract

The immature cerebral cortex self-organizes into local neuronal clusters long before it is activated by patterned sensory inputs1. In the cortical anlage of newborn mammals, neurons coassemble through electrical or chemical synapses either spontaneously2,3,4 or by activation of transmitter-gated receptors5,6. The neuronal network and the cellular mechanisms underlying this cortical self-organization process during early development are not completely understood. Here we show in an intact in vitro preparation of the immature mouse cerebral cortex that neurons are functionally coupled in local clusters by means of propagating network oscillations in the beta frequency range. In the newborn mouse, this activity requires an intact subplate and is strongly synchronized within a cortical column by gap junctions. With the developmental disappearance of the subplate at the end of the first postnatal week7, activation of NMDA (N-methyl-d-aspartate) receptors in the immature cortical network is essential to generate this columnar activity pattern. Our findings show that during a brief developmental period the cortical network switches from a subplate-driven, gap-junction-coupled syncytium to a synaptic network acting through NMDA receptors to generate synchronized oscillatory activity, which may function as an early functional template for the development of the cortical columnar architecture.

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: Carbachol-induced network oscillations in the in vitro intact cerebral cortex of a P2 mouse.
Figure 2: Pharmacology of cholinergic oscillations in neonatal and young mouse cerebral cortex.
Figure 3: Role of subplate neurons in cholinergic oscillations in the neonatal cerebral cortex.
Figure 4: Dye-coupling and electrical coupling between subplate neurons.

Similar content being viewed by others

References

  1. Katz, L. C. & Crowley, J. C. Development of cortical circuits: lessons from ocular dominance columns. Nature Rev. Neurosci. 3, 34–42 (2002)

    Article  CAS  Google Scholar 

  2. Yuste, R., Peinado, A. & Katz, L. C. Neuronal domains in developing neocortex. Science 257, 665–669 (1992)

    Article  ADS  CAS  Google Scholar 

  3. Garaschuk, O., Linn, J., Eilers, J. & Konnerth, A. Large-scale oscillatory calcium waves in the immature cortex. Nature Neurosci. 3, 452–459 (2000)

    Article  CAS  Google Scholar 

  4. Khazipov, R. et al. Early motor activity drives spindle bursts in the developing somatosensory cortex. Nature 432, 758–761 (2004)

    Article  ADS  CAS  Google Scholar 

  5. Peinado, A. Traveling slow waves of neural activity: a novel form of network activity in developing neocortex. J. Neurosci. 20, NIL1–NIL6 (2000)

    Article  MathSciNet  Google Scholar 

  6. Flint, A. C., Dammerman, R. S. & Kriegstein, A. R. Endogenous activation of metabotropic glutamate receptors in neocortical development causes neuronal calcium oscillations. Proc. Natl Acad. Sci. USA 96, 12144–12149 (1999)

    Article  ADS  CAS  Google Scholar 

  7. Price, D. J., Aslam, S., Tasker, L. & Gillies, K. Fates of the earliest generated cells in the developing murine neocortex. J. Comp. Neurol. 377, 414–422 (1997)

    Article  CAS  Google Scholar 

  8. Kilb, W. & Luhmann, H. J. Carbachol-induced network oscillations in the intact cerebral cortex of the newborn rat. Cereb. Cortex 13, 409–421 (2003)

    Article  Google Scholar 

  9. Cruikshank, S. J. et al. Potent block of Cx36 and Cx50 gap junction channels by mefloquine. Proc. Natl Acad. Sci. USA 101, 12364–12369 (2004)

    Article  ADS  CAS  Google Scholar 

  10. Yuste, R., Nelson, D. A., Rubin, W. W. & Katz, L. C. Neuronal domains in developing neocortex: mechanisms of coactivation. Neuron 14, 7–17 (1995)

    Article  CAS  Google Scholar 

  11. Voigt, T., Opitz, T. & De Lima, A. D. Synchronous oscillatory activity in immature cortical network is driven by GABAergic preplate neurons. J. Neurosci. 21, 8895–8905 (2001)

    Article  CAS  Google Scholar 

  12. Hanganu, I. L., Kilb, W. & Luhmann, H. J. Functional synaptic projections onto subplate neurons in neonatal rat somatosensory cortex. J. Neurosci. 22, 7165–7176 (2002)

    Article  CAS  Google Scholar 

  13. Friauf, E., McConnell, S. K. & Shatz, C. J. Functional synaptic circuits in the subplate during fetal and early postnatal development of cat visual cortex. J. Neurosci. 10, 2601–2613 (1990)

    Article  CAS  Google Scholar 

  14. Hanganu, I. L. & Luhmann, H. J. Functional nicotinic acetylcholine receptors on subplate neurons in neonatal rat somatosensory cortex. J. Neurophysiol. 92, 189–198 (2004)

    Article  CAS  Google Scholar 

  15. Mechawar, N. & Descarries, L. The cholinergic innervation develops early and rapidly in the rat cerebral cortex: A quantitative immunocytochemical study. Neuroscience 108, 555–567 (2001)

    Article  CAS  Google Scholar 

  16. Traub, R. D., Bibbig, A., LeBeau, F. E., Buhl, E. H. & Whittington, M. A. Cellular mechanisms of neuronal population oscillations in the hippocampus in vitro. Annu. Rev. Neurosci. 27, 247–278 (2004)

    Article  CAS  Google Scholar 

  17. Beierlein, M., Gibson, J. R. & Connors, B. W. A network of electrically coupled interneurons drives synchronized inhibition in neocortex. Nature Neurosci. 3, 904–910 (2000)

    Article  CAS  Google Scholar 

  18. Kandler, K. & Katz, L. C. Coordination of neuronal activity in developing visual cortex by gap junction-mediated biochemical communication. J. Neurosci. 18, 1419–1427 (1998)

    Article  CAS  Google Scholar 

  19. Montoro, R. J. & Yuste, R. Gap junctions in developing neocortex: a review. Brain Res. Rev. 47, 216–226 (2004)

    Article  CAS  Google Scholar 

  20. Corlew, R., Bosma, M. M. & Moody, W. J. Spontaneous, synchronous electrical activity in neonatal mouse cortical neurons. J. Physiol. (Lond.) 560, 377–390 (2004)

    Article  CAS  Google Scholar 

  21. Connors, B. W., Bernardo, L. S. & Prince, D. A. Coupling between neurons of the developing rat neocortex. J. Neurosci. 3, 773–782 (1983)

    Article  CAS  Google Scholar 

  22. Ghosh, A. & Shatz, C. J. Involvement of subplate neurons in the formation of ocular dominance columns. Science 255, 1441–1443 (1992)

    Article  ADS  CAS  Google Scholar 

  23. Kanold, P. O., Kara, P., Reid, R. C. & Shatz, C. J. Role of subplate neurons in functional maturation of visual cortical columns. Science 301, 521–525 (2003)

    Article  ADS  CAS  Google Scholar 

  24. Fox, K., Schlaggar, B. L., Glazewski, S. & O'Leary, D. D. M. Glutamate receptor blockade at cortical synapses disrupts development of thalamocortical and columnar organization in somatosensory cortex. Proc. Natl Acad. Sci. USA 93, 5584–5589 (1996)

    Article  ADS  CAS  Google Scholar 

  25. Lee, L. J., Iwasato, T., Itohara, S. & Erzurumlu, R. S. Exuberant thalamocortical axon arborization in cortex-specific NMDAR1 knockout mice. J. Comp. Neurol. 485, 280–292 (2005)

    Article  CAS  Google Scholar 

  26. Singer, W. Development and plasticity of cortical processing architectures. Science 270, 758–764 (1995)

    Article  ADS  CAS  Google Scholar 

  27. Buzsáki, G. & Draguhn, A. Neuronal oscillations in cortical networks. Science 304, 1926–1929 (2004)

    Article  ADS  Google Scholar 

  28. Hanganu, I. L., Kilb, W. & Luhmann, H. J. Spontaneous synaptic activity of subplate neurons in neonatal rat somatosensory cortex. Cereb. Cortex 11, 400–410 (2001)

    Article  CAS  Google Scholar 

  29. LoTurco, J. J. & Kriegstein, A. R. Clusters of coupled neuroblasts in embryonic neocortex. Science 252, 563–566 (1991)

    Article  ADS  CAS  Google Scholar 

  30. Rice, F. L. & Van der Loos, H. Development of the barrels and barrel field in the somatosensory cortex of the mouse. J. Comp. Neurol. 171, 545–560 (1977)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank A. Draguhn, V. Lessmann and W. Singer for comments on the manuscript; Roche for the gift of mefloquine; and B. Krumm for technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft and the MAIFOR programme of the Medical Faculty at the University of Mainz.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Heiko J. Luhmann.

Ethics declarations

Competing interests

Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.

Supplementary information

Supplementary Notes

This file contains Supplementary Figures 1–4, Supplementary Table 1 and Supplementary Methods. (DOC 3918 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dupont, E., Hanganu, I., Kilb, W. et al. Rapid developmental switch in the mechanisms driving early cortical columnar networks. Nature 439, 79–83 (2006). https://doi.org/10.1038/nature04264

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature04264

This article is cited by

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.

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