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ABSTRACT Neurons in the mammalian neocortex are organized into functional columns1,2. Within a column, highly specific synaptic connections are formed to ensure that similar physiological

properties are shared by neuron ensembles spanning from the pia to the white matter. Recent studies indicate that synaptic connectivity in the neocortex is sparse and highly

specific3,4,5,6,7,8 to allow even adjacent neurons to convey information independently9,10,11,12. How this fine-scale microcircuit is constructed to create a functional columnar architecture

at the level of individual neurons largely remains a mystery. Here we investigate whether radial clones of excitatory neurons arising from the same mother cell in the developing neocortex

serve as a substrate for the formation of this highly specific microcircuit. We labelled ontogenetic radial clones of excitatory neurons in the mouse neocortex by _in utero_ intraventricular

injection of enhanced green fluorescent protein (EGFP)-expressing retroviruses around the onset of the peak phase of neocortical neurogenesis. Multiple-electrode whole-cell recordings were

performed to probe synapse formation among these EGFP-labelled sister excitatory neurons in radial clones and the adjacent non-siblings during postnatal stages. We found that radially

aligned sister excitatory neurons have a propensity for developing unidirectional chemical synapses with each other rather than with neighbouring non-siblings. Moreover, these synaptic

connections display the same interlaminar directional preference as those observed in the mature neocortex. These results indicate that specific microcircuits develop preferentially within

ontogenetic radial clones of excitatory neurons in the developing neocortex and contribute to the emergence of functional columnar microarchitectures in the mature neocortex. Access through

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(2006) Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We thank A. L. Joyner, J. Kaltschmidt, Y. Hayashi and Y. Chin for comments on the manuscript; and S. C. Noctor and

F. H. Gage for providing the 293gp NIT–GFP retrovirus packaging cell line; and the Shi laboratory members for insightful discussion. We are grateful for support from the March of Dimes

Foundation, the Whitehall Foundation, the Klingenstein Foundation, the DANA Foundation, the Autism Speaks Foundation, the National Alliance for Research on Schizophrenia and Depression

(NARSAD) and the National Institutes of Health (to S.-H.S.). AUTHOR CONTRIBUTIONS Y.-C.Y. and S.-H.S. conceived the experiments. Y.-C.Y. conducted the electrophysiology and imaging

experiments. R.S.B and X.W. helped with _in utero_ virus injection. Y.-C.Y. and S.-H.S. analysed the data and wrote the manuscript. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS *

Developmental Biology Program, Memorial Sloan Kettering Cancer Centre, 1275 York Avenue, Yong-Chun Yu, Ronald S. Bultje, Xiaoqun Wang & Song-Hai Shi * Department of Pharmacology, Weill

Medical College of Cornell University, 445 East 69th Street, New York, New York 10065, USA, Ronald S. Bultje Authors * Yong-Chun Yu View author publications You can also search for this

author inPubMed Google Scholar * Ronald S. Bultje View author publications You can also search for this author inPubMed Google Scholar * Xiaoqun Wang View author publications You can also

search for this author inPubMed Google Scholar * Song-Hai Shi View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to

Song-Hai Shi. SUPPLEMENTARY INFORMATION SUPPLEMENTARY FIGURES This file contains Supplementary Figures 1-5 with Legends (PDF 1812 kb) POWERPOINT SLIDES POWERPOINT SLIDE FOR FIG. 1 POWERPOINT

SLIDE FOR FIG. 2 POWERPOINT SLIDE FOR FIG. 3 POWERPOINT SLIDE FOR FIG. 4 RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Yu, YC., Bultje, R., Wang, X.

_et al._ Specific synapses develop preferentially among sister excitatory neurons in the neocortex. _Nature_ 458, 501–504 (2009). https://doi.org/10.1038/nature07722 Download citation *

Received: 22 October 2008 * Accepted: 11 December 2008 * Published: 08 February 2009 * Issue Date: 26 March 2009 * DOI: https://doi.org/10.1038/nature07722 SHARE THIS ARTICLE Anyone you

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