Clear brains you say??

Karl Deisseroth
Karl Deisseroth

The interwebs have been abuzz this week about a new technique published in Nature coming from the Deisseroth Lab at Stanford (formerly of optogenetics fame). Now he’s the optogenetics guy AND the CLARITY guy, come on Karl leave something for the rest of us! Anyway, the new method allows entire brains, that have been removed from their respective skulls, to be processed into hydrogel hybrids that are optically clear and able to be labeled and observed all the way to their very center. This video is an example of a CLARITY processed mouse brain that is labeled with Thy1-GFP (green fluorescent protein expressed in ~10% of neurons). You can see individual neural cell bodies (the small round dots) and the projections from individual neurons (long thin fibers).

By replacing the fatty tissue of the brain with hydrogel, the properties of the brain that once made it opaque are modified so that the tissue is now transparent. It is also totally preserved while also permeable to larger molecules like antibodies. You can serially label the brain to look at all sorts of markers without damaging the tissue. While neuroscientists everywhere are excited to begin “clearing” the brains of their organism of choice, I think the most exciting opportunity is for exploring the human brain.

There are a great number of human brains that have been donated to scientific research. These brains have been carefully fixed and stowed away awaiting a future that is prepared to examine these samples without destroying them. Every once in a while a small sample is taken to prepare DNA and examine the genome of these diseased or healthy brains. Otherwise, scientists are reluctant to perform risky, or even common place experiments on these tissues for fear of destroying a precious resource. Now with the CLARITY technique, these brains could be converted to a stable hydrogel format and then a series of markers (labeling neural connections, A-beta, or Tau) could be examined in these brains and all of the images could then be part of a data set about this particular brain. This seems like a way to allow scientists to get the most bang for their buck from each precious human sample. To me, this is the most exciting implication of the CLARITY technique.

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