Stanford team transforms brain into transparent wonder

CLARITY provides a detailed view of the brain.--Courtesy of Stamford

A Stanford University research team has concocted a new process that allowed them to make a mouse's brain completely transparent to the point of seeing detailed neuronal networks inside. The same technique, dubbed CLARITY, worked on zebrafish and human brain samples too.

Details of these eventful chemical engineering and neuroscience accomplishments are published in the journal Nature, and The New York Times highlighted the findings in a vivid story published this week.

Their achievement stands to upend a whole lot more than the study of the brain, which is typically performed post-mortem through slices or sections. On the one hand, this advance in brain imaging will allow for much more detailed studies of the brain, which is opaque--how it works and what drives it, offering details and depth that dissection and other imaging equipment don't allow. One of the paper's lead authors--psychiatrist Karl Deisseroth--also just happened to be one of a several specialists commissioned by President Barack Obama to outline goals of his new $100 million brain research initiative.

But the technology has potential uses that could allow for more precise imaging of tissue samples and other biological systems, the researchers note, opening up huge possibilities for research and diagnostics alike down the line. Dr. Thomas Insel, director of the National Institute of Mental Health, which helped fund the study, told The New York Times he sees the imaging technique as eventually helping to better understand diseases such as autism, post-traumatic stress disorder, bipolar disorder, and more.

To create a transparent brain, the research team replaced the brain's lipids with a hydrogel. Specifically, the brain is put into a watery pool of hydrogel monomers. Add a little heat to slightly above body temperature, and the hydrogel molecules take shape into a mesh that permeates all through the brain, supporting the tissue but avoiding the lipids. Electrophoresis helps extract the lipids, leaving the brain and all of its details intact, enabling 3-D imaging and molecular analysis to the point of neural circuits and their wiring, and beyond. Fluorescent antibodies that attach themselves to specific antibodies make the structures light up.

Interestingly, they can flush out the fluorescent antibodies and then use new ones in order to hit different molecular targets. The process even worked on intact brains preserved for many years. Deisseroth, in a statement, said that being able to study an intact brain with the detail that CLARITY creates helps addresses "a major unmet goal in biology." He expects researchers to use the technique to study "intrasystem relationships" in their future work.

- read the release
- here's the NYT story (sub. req)
- check out the Nature abstract

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