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Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly

Nature volume 486, pages 113–117 (2012)Cite this article

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Abstract

Radial glial cells are the primary neural progenitor cells in the developing neocortex1. Consecutive asymmetric divisions of individual radial glial progenitor cells produce a number of sister excitatory neurons that migrate along the elongated radial glial fibre, resulting in the formation of ontogenetic columns2,3,4. Moreover, sister excitatory neurons in ontogenetic columns preferentially develop specific chemical synapses with each other rather than with nearby non-siblings5. Although these findings provide crucial insight into the emergence of functional columns in the neocortex, little is known about the basis of this lineage-dependent assembly of excitatory neuron microcircuits at single-cell resolution. Here we show that transient electrical coupling between radially aligned sister excitatory neurons regulates the subsequent formation of specific chemical synapses in the neocortex. Multiple-electrode whole-cell recordings showed that sister excitatory neurons preferentially form strong electrical coupling with each other rather than with adjacent non-sister excitatory neurons during early postnatal stages. This preferential coupling allows selective electrical communication between sister excitatory neurons, promoting their action potential generation and synchronous firing. Interestingly, although this electrical communication largely disappears before the appearance of chemical synapses, blockade of the electrical communication impairs the subsequent formation of specific chemical synapses between sister excitatory neurons in ontogenetic columns. These results suggest a strong link between lineage-dependent transient electrical coupling and the assembly of precise excitatory neuron microcircuits in the neocortex.

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Figure 1: Gap-junction-mediated electrical coupling between sister excitatory neurons in neonatal neocortical ontogenetic columns.
Figure 2: Preferential formation of strong electrical coupling between sister excitatory neurons in neonatal neocortical ontogenetic columns.
Figure 3: Electrical coupling promotes action potential generation and synchronous firing of sister excitatory neurons in neonatal neocortical ontogenetic columns.
Figure 4: Preferential electrical coupling is required for chemical synapse formation between sister excitatory neurons in neocortical ontogenetic columns.

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Acknowledgements

We thank the following: C. I. Bargmann, Y. Dan, A. L. Joyner, K. M. Hively and Y. Chin for comments on the manuscript; F. H. Gage for the 293gp NIT–GFP package cell line; E. C. Holland for nestin-TVA transgenic mice; and members of the Shi and Yu laboratories for their input. This work was supported by grants from the Ministry of Science and Technology of China (2012CB966300), the Natural Science Foundation of China (31121061 and 31070947), the Pujiang Talent Project of the Shanghai Science and Technology Committee (10PJ1400700), the Foundation of the Ministry of Education of China (20100071120061) (Y.-C.Y.), the National Institutes of Health (R01DA024681 and R21NS072483 (S.-H.S.), R21MH083624 (S.-H.S. and K.H.) and R01GM065947 (G.E.S.)), the McKnight Foundation and the March of Dimes Foundation (S.-H.S.).

Author information

Author notes

  1. Yong-Chun Yu and Shuijin He: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai 200032, China,

    Yong-Chun Yu, Yinghui Fu, Xing-Hua Yao & Jian Ma

  2. Developmental Biology Program, Memorial Sloan-Kettering Cancer Centre, 1275 York Avenue, New York, New York 10065, USA,

    Shuijin He, She Chen, Keith N. Brown, Kate P. Gao & Song-Hai Shi

  3. Neuroscience Graduate Program, Weill Cornell Medical College, 1230 York Avenue, New York, New York 10065, USA,

    Keith N. Brown, Kate P. Gao & Song-Hai Shi

  4. National Centre for Microscopy and Imaging Research and Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0608, USA,

    Gina E. Sosinsky

  5. Department of Biomedical Informatics, Comprehensive Cancer Center Biomedical Informatics Shared Resource, The Ohio State University, 333 West 10th Avenue, Columbus, Ohio 43210, USA,

    Kun Huang

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Contributions

Y.-C.Y., S.H. and S.-H.S. conceived the project. Y.-C.Y. and S.H. conducted the electrophysiology and morphology reconstruction experiments. S.C., Y.F. and K.N.B. generated viruses and performed in utero virus injections and morphological reconstructions. X.-H.Y., J.M. and K.P.G. performed immunohistochemistry and morphological reconstruction experiments. G.E.S. helped with CX26-carrying retrovirus engineering. K.H. performed cross-correlogram analysis. Y.-C.Y., S. H. and S.-H.S. analysed the data, interpreted the results and wrote the manuscript. All authors edited the manuscript.

Corresponding authors

Correspondence to Yong-Chun Yu, Shuijin He or Song-Hai Shi.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figures

This file contains Supplementary Figures 1-8. (PDF 3136 kb)

Supplementary Movie 1

In this movie file we see the localization of Cx26 puncta (red) at the dendrosomatic contacts of sister excitatory neurons in ontogenetic columns expressing EGFP (green). The three-dimensional image was reconstructed using Imaris and the play rate is 25 frames per second. (MOV 5407 kb)

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Yu, YC., He, S., Chen, S. et al. Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly. Nature 486, 113–117 (2012). https://doi.org/10.1038/nature10958

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