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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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.
Reprints and permissions information is available at npg.nature.com/reprintsandpermissions. The authors declare no competing financial interests.
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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). https://doi.org/10.1038/nature04264
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