Brains made of fruit and toothpaste by Kyle Bean.
Pseudo-colour scanning electron micrograph showing an axon terminal broken open to reveal synaptic vesicles (blue and orange). Tina Carvalho/ NIH-NIGMS.
Seeing the Brain With New CLARITY
A new brain imaging technique called CLARITY allows neural structures to be reconstructed in three dimensions better than ever before. It does so by turning the brain “transparent”.
Truly understanding the inner workings of the brain means studying not only how individual neurons function, but also how they are wired together. Even with techniques like the beautiful “brainbow”, untangling spaghetti-like long-range connections has proven difficult.
Stanford University neuroscientists have taken a step in that direction with their new CLARITY method. Neurons and other cells are normally labeled by sticking fluorescent tags on various proteins and other molecules that a researcher wants to study. That way we can literally see where and how they function. But looking into a three-dimensional brain is like peering into murky water: the fatty cell membranes and neuron sheaths just get in the way.
The Stanford researchers immobilized these mouse brains in a gel, then washed away all the murky muck. This left all the connections and proteins in their right place, free to be labeled in a clear block of brain Jell-O.
For more: Head over to Nature News to read more, and be sure to watch their great, detailed video to find out more about how it was done. If you’re interested, here’s the research paper in this week’s Nature.
CLARITY makes mouse brain completely transparent. Kwanghun Chung and Karl Deisseroth. Howard Hughes Medical Institute/Stanford University.
Human astrocytes (green) are about 20x bigger and far more complex than mouse astrocytes (red). When grafted into the mouse brain, they boost the animals’ ability to learn. Image: Maiken Nedergaard and Steve Goldman/ University of Rochester Medical Center
A whole brain activity map: This short clip shows the firing patterns of approximately 90,000 individual neurons in the brain of a zebrafish larva over the course of an hour.
High magnification image of a mouse cerebral cortex reconstructed with serial section electron microscopy. Bobby Kasthuri/ Daniel Berger/ Sebastian Seung/ Jeff Lichtman (via Scientific American)
Original colour drawing by Korbinian Brodmann, showing cortical areas in the European ground squirrel Spermophilus citellus (MPI Brain Research Archive)
Human hippocampus stained with a method pioneered by Italian physician Camillo Gogli in 1873.Golgi discovered a chemical reaction that allowed him to examine nervous tissue in much greater detail than ever before. For some reason, hardening a piece of brain in potassium dichromate, and subsequently dousing it with silver nitrate, dyed only a few cell bodies and their respective projections in the tissue sample, revealing their complete structures and exact arrangement within the unstained tissue. If the reaction had stained all the neurons in a sample, Golgi would have been left with an unfathomable black blotch, as though someone had spilled a bottle of ink. Instead, his technique yielded neat black silhouettes against a translucent yellow background.
More in Scientific American’s Know Your Neurons series.
Diffusion spectrum MRI image of the human brain showing three dimensional grid structure of white matter tracts. From Wedeen, et al (2012).
Confocal micrograph of a ‘Brainbow' mouse hippocampus. By Jean Livet.
Quadruple fluorescence image of the mouse retina, showing optic nerve axons and glia stained red and green, respectively, actin in endothelial cells of the blood vessel walls stained blue and nucleic acids stained orange. By Thomas Deerinck/ NCMIR/ Cell.