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Blockheads No More: New Technology Creates the See-Through Brain [Video]

The views expressed are those of the author and are not necessarily those of Scientific American.

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Transparent ("CLARITY-fied") mouse brain

Karl Deisseroth is a pioneer in optogenetics, the technology that has taken neuroscience by storm by enabling the use of optical and genetic methods to precisely control the switching on and off of individual neurons and brain circuits.

Deisseroth and his team at Stanford have now come up with an entirely new method to explore the brain that  U.S. National Institute of Mental Health director Thomas Insel told Nature represents “probably one of the most important advances for doing neuroanatomy in decades.”

As its name suggests, it is a means of making the post-mortem brain of a mouse or human transparent, a boon to researchers who wish to literally get a clearer picture of the mess of wiring in neural tissue without having to digitally stack images of tiny brain slices in a computer. The paper in our sister publication Nature went live on April 10 so  Scientific American decided to talk with Deisseroth about the advance.

What is CLARITY?

Clarity is the process of exchanging natural tissue components for components from outside the body to achieve new visibility, access, or function. For example, the CLARITY method described in the Nature paper involves exchanging native lipids for an artificial hydrogel, that provides transparency, firmness, and the ability to label tissues.

How do you get it to work?

We first build in-place, and from within the tissue, a new firm hydrogel infrastructure that retains proteins and nucleic acids but excludes lipids, which can then be vigorously removed with ionic detergents and electrophoresis

What will be the benefit for brain and other researchers?

This enables researchers to study complex biological systems with high resolution without taking them apart. This not only saves a great deal of time and effort but serves useful scientific purposes as well, by allowing assessment of joint relationships among the different elements within a complex system– for example, brainwide connection patterns coupled with panels of molecular labels.

How does it fit with your other work on techniques to understand neural circuits (optogenetics)?

It’s independent from our optogenetics technology, but the two could work together. For example, one could clarify a brain from an animal in which optogenetic control had been delivered (over neurons expressing an opsin fused to a fluorescent protein as we usually have it configured) and which had resulted in a known behavioral change (a mouse that stops feeding after receiving an electrical shock, for instance).  One could thereby map the local and global connectivity of those same neurons in the same animal known to cause behavioral change to a known extent.

Do you think you’ll ever be able to do something like this in a live animal?

The CLARITY method described in the Nature paper is not compatible with life since the lipids are essential for life, but other CLARITY approaches could be.


Image Source: Kwanghu Chung and Karl Deisseroth, Howard Hughes Medical Institute/Stanford University


Gary Stix About the Author: Gary Stix, a senior editor, commissions, writes, and edits features, news articles and Web blogs for SCIENTIFIC AMERICAN. His area of coverage is neuroscience. He also has frequently been the issue or section editor for special issues or reports on topics ranging from nanotechnology to obesity. He has worked for more than 20 years at SCIENTIFIC AMERICAN, following three years as a science journalist at IEEE Spectrum, the flagship publication for the Institute of Electrical and Electronics Engineers. He has an undergraduate degree in journalism from New York University. With his wife, Miriam Lacob, he wrote a general primer on technology called Who Gives a Gigabyte? Follow on Twitter @@gstix1.

The views expressed are those of the author and are not necessarily those of Scientific American.

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  1. 1. bicyclemichaela 4:24 pm 04/10/2013

    Nifty technique. Should yield many impressive results. Congratulations to the team at Stanford.

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  2. 2. tuned 6:18 pm 04/10/2013

    “One could thereby map the local and global connectivity of those same neurons in the same animal known to cause behavioral change to a known extent”.
    As science it’s great.
    Morally it could be as dangerous as genetic manipulation that created biological warfare departments.

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  3. 3. apexis 3:26 am 04/11/2013

    New technologies appear to popularity, there is often a very long way to go.

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  4. 4. osuzanna7 5:49 pm 04/14/2013

    This is beautiful!

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