Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly

Yong-Chun Yu ^{1, 6}, Shuijin He ^{2, 6}, She Chen ², Yinghui Fu ¹, Keith N. Brown ^{2, 3}, Xing-Hua Yao ¹, Jian Ma ¹, Kate P. Gao ^{2, 3}, Gina E. Sosinsky ⁴, Kun Huang ⁵ and Song-Hai Shi ^{2, 3}

¹ Institute of Neurobiology, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, China; ² Developmental Biology Program, Memorial Sloan-Kettering Cancer Centre, 1275 York Avenue, New York, NY 10065; ³ Neuroscience Graduate Program, Weill Cornell Medical College, 1230 York Avenue, New York, NY 10065; ⁴ National Centre for Microscopy and Imaging Research and Department of Neurosciences, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0608; ⁵ Department of Biomedical Informatics, Comprehensive Cancer Center Biomedical Informatics Shared Resource, The Ohio State University, 333 West 10^th Avenue, Columbus, OH 43210, USA; ⁶ These authors contributed equally to this work

Radial glial cells are the primary neural progenitor cells in the developing neocortex ¹. 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 columns ^2-4. Moreover, sister excitatory neurons in ontogenetic columns preferentially develop specific chemical synapses with each other rather than with nearby non-siblings ⁵. While these findings provide crucial insights into the emergence of functional columns in the neocortex, little is known about the basis for this lineage-dependent assembly of excitatory neuron microcircuits with 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 revealed 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, while this electrical communication largely disappears prior to the appearance of chemical synapses, its blockade impairs the subsequent formation of specific chemical synapses between sister excitatory neurons in ontogenetic columns. These results suggest a strong link between a lineage-dependent transient electrical coupling and the assembly of precise excitatory neuron microcircuits in the neocortex.

Nature Year published: (2012) DOI: doi:10.1038/nature10958

Received 22 September 2011, Accepted 14 February 2012, Published online02 May 2012

* Correspondence and request for materials should be addressed to Y.-C.Y. (ycyu@fudan.edu.cn), S. H. (hes@mskcc.org) or S.-H.S. (shis@mskcc.org)

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My name is Wang Luhong, an undergraduate student in Fudan. My first exposure to research started from the second summer vacation, when I got into Dr. Yong-Chun Yu’s group in Institute of Neuroscience in Fudan University. It was an unforgettable experience in getting involved in the cutting-edge research to learn techniques like patch-clamp, immunohistochemistry staining, etc.; and it has also deepened my understanding of development, a precise and complex process which is worth my time and effort.

I started the first project from Mar. to Jun. in 2011, focusing on somatodendritic morphology of subplate neurons in different stages of mammalian postnatal development. Since September 2011, I began to design Chr2-dsRed retroviral vectors in order to reveal the functional organization of cloning pyramidal cell and local interneuron. The rich internship experience in Dr. Yu’s Lab undoubtedly eases my transition into graduate research, and has enhanced my understanding of development and neuroscience.

Scientifically speaking, my internship in Yu Lab, an enriched environment, is the most important experience during my development. Thanks for my mentor Dr. Yu’s help. I get the offer of admission from University of Michigan for the Program in Biomedical Sciences (PIBS). I’m looking forward to the future academic life there and also feel truly thankful for the knowledge I have learned in Dr.Yu’s Lab here.

My name is Wang Luhong, an undergraduate student in Fudan. My first
exposure to research started from the second summer vacation, when I
got into Dr. Yong-Chun Yu’s group in Institute of Neuroscience in
Fudan University. It was an unforgettable experience in getting
involved in the cutting-edge research to learn techniques like
patch-clamp, immunohistochemistry staining, etc.; and it has also
deepened my understanding of development, a precise and complex
process which is worth my time and effort.

I started the first project from Mar. to Jun. in 2011, focusing on
somatodendritic morphology of subplate neurons in different stages of
mammalian postnatal development. Since September 2011, I began to
design Chr2-dsRed retroviral vectors in order to reveal the functional
organization of cloning pyramidal cell and local interneuron. The rich
internship experience in Dr. Yu’s Lab undoubtedly eases my transition
into graduate research, and has enhanced my understanding of
development and neuroscience.

Scientifically speaking, my internship in Yu Lab, an enriched
environment, is the most important experience during my development.
Thanks for my mentor Dr. Yu’s help, I get the offer of admission from
University of Michigan for the Program in Biomedical Sciences (PIBS).
I’m looking forward to the future academic life there and also feel
truly thankful for the knowledge I have learned in Dr.Yu's Lab here.