New transparency in brain imaging

To truly understand the brain, one must know its structure over several orders of magnitude in length. Neurons just a micron or so in diameter connect with one another and form circuits spanning millimeters or more. Mice and other animals can be genetically engineered so that their brain cells synthesize proteins that fluoresce in various colors; individual cells in fluorescence images can then be tracked from end to end. But brain tissue is opaque to light. To image neurons beneath the surface, researchers slice the brain into thin sections and thereby destroy some of its large-scale structure. The opacity is almost entirely due to the lipid bilayers that make up the cell and organelle membranes. Now, Karl Deisseroth and colleagues at Stanford University have developed a technique for removing those membranes—rendering the brain optically transparent—without destroying the tissue or the fluorescent proteins it contains. Their strategy is to infuse the brain with an organic polymer that maintains the tissue’s structural stability even as the cell membranes are washed away. The researchers find that they can image up to 4 mm beneath the surface of the newly transparent brain with negligible loss of resolution. (Adult mouse brains, for comparison, are just 5–6 mm thick.) As a result, they can image the brain’s three-dimensional structure on both large and small scales, as shown in the figure. Furthermore, the transparent brain tissue is also macromolecule-permeable, so it can be infused with fluorescent proteins bound to antibodies, which attach to biomolecules of interest. That capability allows the researchers to take fluorescence images of the neurons in preserved human brains, which can’t be genetically engineered for obvious reasons. (K. Chung et al., Nature, doi:10.1038/nature12107.)—Johanna Miller