Stanford researchers, led by Kwanghun Chung, have developed an amazing tool for seeing the inner workings of the brain. In an obvious attempt to fit their chosen acronym of CLARITY (and an excellent acronym it is), they named their technique Clear Lipid-exchanged Anatomically Rigid Imaging/immunostaining-compatible Tissue hYdrogel. Nicely done.
CLARITY transformation of a mouse brain at left into a transparent but still intact brain at right. Shown superimposed over a quote from the great Spanish neuroanatomist Ramon y Cajal.
Credit: Kwanghun Chung and Karl Deisseroth, Howard Hughes Medical Institute/Stanford University.
So, how do you make a brain transparent? Here’s the extremely simplified recipe:
- Step one: Infuse your brain with a mix of chemicals (acrylamide, bisacrylamide and formaldehyde) that bind to proteins, nucleic acids and small molecules, but critically, not to lipids (fats)
- Step two: Allow the chemicals to solidify into a gel that permeates the entire brain. The molecules listed in step one are locked in place by this acrylamide matrix.
- Step three: Run an electric current through the brain to eliminate everything not attached to the acrylamide gel (i.e. the light-reflecting lipids). The result is a totally transparent brain, as shown above.
- Step four: Add your stain or stains of choice.
Three-dimensional view of stained hippocampus showing:
fluorescent-expressing neurons (green)
connecting interneurons (red)
supporting glia (blue).
Credit: Courtesy of the Deisseroth lab.
What can be done with this technique? A better question might be 'what can't you do with it?' Not only could you directly compare the brain structures of people with and without diseases like Alzheimer’s, cancer or autism, but you could see how different parts of the brain interact with each other. Unlike with current brain staining technologies, you can look at entire brains rather than only at thin slices of brain tissue.
CLARITY allows imaging through the entire intact brain without sectioning. Shown is yellow fluorescent protein labeling of chiefly projection (Thy1) neurons in an entire intact mouse brain.
CREDIT: Kwanghun Chung and Karl Deisseroth, Howard Hughes Medical Institute/Stanford University.
Not enough pretty pictures? How about a video:
In case you're wondering, this technique will work with any organs, not just brains. Brains are just the coolest thing to look at.
More details at Science Daily, Not Exactly Rocket Science and the L.A. Times.
Chung, K., Wallace, J., Kim, S., Kalyanasundaram, S., Andalman, A., Davidson, T., Mirzabekov, J., Zalocusky, K., Mattis, J., Denisin, A., Pak, S., Bernstein, H., Ramakrishnan, C., Grosenick, L., Gradinaru, V., & Deisseroth, K. (2013). Structural and molecular interrogation of intact biological systems Nature DOI: 10.1038/nature12107.