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Rapid developmental switch in the mechanisms driving early cortical columnar networks


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.

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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.


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

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  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)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  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)

    MathSciNet  Article  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)

    ADS  CAS  Article  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)

    CAS  Article  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)

    ADS  CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    CAS  Article  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)

    CAS  Article  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)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  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)

    ADS  CAS  Article  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)

    ADS  CAS  Article  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)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  Google Scholar 

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

    ADS  Article  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)

    CAS  Article  Google Scholar 

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

    ADS  CAS  Article  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)

    CAS  Article  Google Scholar 

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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.

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Correspondence to Heiko J. Luhmann.

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

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