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As Clear as a Cell: Researchers See Deeper into Tissue than Ever Before

  • Brendan Brinkman (a1)

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Researchers have long sought to visualize neural projections and other features of animal brains by imaging them using light microscopes. Connectomics studies strive to elucidate the connections among nerve cells, but brain is dense, and gray matter is tremendously light-scattering. So scientists have not been able to peer as deeply into brain tissue as is necessary to view its complex connections and structures without cutting brain tissue into thin sections. The slicing causes damage that makes it even more difficult to reconstruct exactly how nervous system structures are interconnected. Issues with light scattering have also limited studies of microvasculature, developmental structures, and other features in mouse embryos and other tissues. Traditional methods of retrograde or anterograde labeling have been able to provide high specificity of connection circuitry, but at the price of losing the organizational context of the network. In addition, there is a limit to the practical number of labels that can be used at once. Even multicolor methods have required serial section reconstruction.

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[1]Denk, W, Strickler, JH, and Webb, WW, Cornell Research Foundation, Inc. United States Patent Number 5034613, Issued July 23, 1991. (Text available online at http://patft .uspto.gov/netacgi/nph-Parser?Sect1=PTO1&Sect2= HITOFF&d=PALL&p=1&u=%2Fnetahtml%2FPTO%2 Fsrchnum.htm&r=1&f=G&l=50&s1=5034613.PN.& OS=PN/5034613&RS=PN/5034613. Accessed April 4, 2012.)
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[3]RIKEN statement available online at http://www.riken.jp/en/pr/press/2011/20110830_3/, August 30, 2011. (Accessed April 4, 2012.)
[4]Chunget al., Nature 496(151) (2013) doi:10.1038/496151a.

As Clear as a Cell: Researchers See Deeper into Tissue than Ever Before

  • Brendan Brinkman (a1)

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