Scientists have created a way to make a human brain transparent, enabling them to take deep three-dimensional tours through the mysterious organ and trace its circuitry down to the molecular level.
The recipe for transforming cadaver brains into see-through research tools stands to accelerate investigations of Alzheimer's disease, schizophrenia and a host of other brain maladies, and already has led to a significant insight into the peculiar characteristics of neurons associated with Down syndrome and autism.
The advance, published online Wednesday by the journal Nature, was described by scientists as "transformative" and just plain "cool." It involves washing away the fat that normally obscures the view of cells and replacing it with a see-through gel to hold everything in place.
"This feat of chemical engineering promises to transform the way we study the brain's anatomy and how disease changes it," said Dr. Thomas R. Insel, director of the National Institute of Mental Health, which funded the research conducted at Stanford University.
Found it at Smithsonian.com, video is courtesy of Nature magazine:
Producing a fully intact, transparent mouse brain (as shown in the image at below) creates all sorts of interesting imaging opportunities. With the fat molecules flushed out, the elements of experimental or clinical interest (neuron networks or genes, for example) are no longer obscured by cell membranes. (In much the same way, zebrafish, with their transparent embryos, are heavily used in many fields of biological research.)
To see the aspects clearly, the researchers added colored chemical markers that specifically attach to certain kinds of molecules. Once this is done, scientists can examine them with a conventional light microscope, or combine multiple images from digital microscopes to create a 3-D rendering.
As a proof-of-concept, in addition to the mouse brain, the research team performed the procedure on small pieces of a deceased autistic person’s brain that had been in storage for 6 years. With specialized chemical markers, they were able to trace individual neurons across large swaths of tissue. They also found atypical ladder-like neuron structures that have also been seen in the brains of animals with autism-like symptoms.
This sort of detailed analysis has previously only been possible by laboriously examining tiny slices of brain with a microscope to infer a full three-dimensional picture. But now, interconnections between different parts of the brain can be seen on a broader level.
A new technique renders a mouse brain (opaque, at left) entirely transparent (at right) for easier imaging.
Image by Kwanghun Chung and Karl Deisseroth, Howard Hughes Medical Institute/Stanford University
The original article in Nature is Structural and molecular interrogation of intact biological systems but as usual you only get to see the abstract and some of the diagrams and videos with subscribing/paying.