October 10, 2011
By RITCHIE S. KING
A group of Japanese neuroscientists is trying to peer into the mind — literally. They have devised a way to turn the brain’s opaque gray matter into a glassy, see-through substance.
The group, based at the government-financed Riken Brain Science Institutein Wako, Japan, has created an inexpensive chemical cocktail that transforms dead biological tissue from a colored mass into what looks like translucent jelly. Soaking brain tissue in the solution makes it easier for neuroscientists to see what’s inside, a step they hope will uncover the physical basis of personality traits, memories and even consciousness.
“I’m very excited about the potential,” said Dr. Atsushi Miyawaki, a researcher on the team, which published its discovery in the journal Nature Neuroscience.
The chemical solution — patented under the name Scale, a phonetic approximation of the Japanese word for “transparent” — could help neuroscientists map the brain’s underlying architecture, though that goal is still a distant one. At the moment, researchers are working to build such a map, called a “connectome,” of mouse brains, which are far less complex than human ones.
Ultimately, this mapping could be conducted on brains of different ages, Dr. Miyawaki said, providing a glimpse into how the organ develops and even how genetic differences might affect that development.
Dr. Miyawaki and his team have yet to try Scale on a human brain — their lab works with mice — but they plan to as soon as the gated process of obtaining a specimen is completed. He expects that the transparency solution will work just as well as it does on mouse brains.
Dr. Jeff Lichtman, a neuroscientist at Harvard University who is involved with theHuman Connectome Project — a multi-institution effort to map a mouse brain, and then a human one — thinks that Scale shows promise and plans to use it in his lab. It looks like a good method for “clearing the brain,” he said in a telephone interview. “Clear brains,” he said. “That’s the big thing.”
The neurons of the brain are “interconnected in a vast and deeply mysterious network of wires, so there’s a wiring diagram,” Dr. Lichtman said. Scientists have to figure that diagram out before they can understand how information flows through it, he continued. If the brain were clarified using a solution like Scale, researchers could trace big sections of the diagram “all in one sitting,” he said, “and that would be terrific.”
Currently, to see brain tissue under a microscope, neuroscientists have to slice it into slivers about the thickness of a human hair, so that light can pass through. To analyze an entire mouse brain this way — a process that Dr. Lichtman’s lab is attempting, but that is nowhere near finished — the organ needs to be divided into roughly a hundred slices, each of which must be passed under a microscope for a snapshot of its cells.
Not only is the process labor-intensive, but the slices of brain can get distorted, and small bits of tissue can get lost. These hard-to-avoid errors can turn the snapshots into deformed puzzle pieces that can’t easily be fitted together into a wiring diagram.
A mouse brain that has been clarified with Scale, on the other hand, is clear enough without thin-slicing, and could be imaged in three big chunks, avoiding these problems, according to Dr. Miyawaki. Because it clarifies tissue without removing water, the solution sustains genetically introduced cell labels — used to differentiate one neuron from the next — in a wet environment like the one in which they originally evolved. The labels are made of proteins that come from jellyfish and corals.
According to Dr. Miyawaki, Scale works much better on young brains than on older ones, which are filled with more hard connective tissue that doesn’t absorb the solution as readily.
So far, Dr. Miyawaki and his team have used the solution only on dead tissue. The next step, he said, is to come up with a formulation that works on living tissue, though for now that is a distant goal.
Scale is not difficult to make: It is a cheap mixture of urea (found in urine and fertilizer), glycerol and detergent. While he and a colleague hold the patent on it, Dr. Miyawaki included the complete recipe in his recently published article and hopes that labs around the world will start using it for brain mapping.
Neuroscientists can’t answer important questions about the brain until they have a map of the neuronal circuit, Dr. Miyawaki said, adding, “and there are many, many important questions.”