Brain tissue models: cryo- (purple) and chemically- fixed (brown) © Graham Knott/EPFL
(August 11, 2015) Using an innovative method, EPFL scientists show that the brain is not as compact as we have thought all along.
To study the fine structure of the brain, including its connections between neurons, the synapses, scientists must use electron microscopes. However, the tissue must first be fixed to prepare it for this high magnification imaging method. This process causes the brain to shrink; as a result, microscope images can be distorted, e.g. showing neurons to be much closer than they actually are. EPFL scientists have now solved the problem by using a technique that rapidly freezes the brain, preserving its true structure. The work is published in eLife.
The shrinking brain
Recent years have seen an upsurge of brain imaging, with renewed interest in techniques like electron microscopy, which allows us to observe and study the architecture of the brain in unprecedented detail. But at the same time, they have also revived old problems associated with how this delicate tissue is prepared before images can be collected.
Typically, the brain is fixed with stabilizing agents, such as aldehydes, and then encased, or embedded, in a resin. However, it has been known since the mid-sixties that this preparation process causes the brain to shrink by at least 30 percent. This in turn, distorts our understanding of the brain’s anatomy, e.g. the actual proximity of neurons, the structures of blood vessels etc.
The freezing brain
A study by Graham Knott at EPFL, led by Natalya Korogod and working with Carl Petersen, has successfully used an innovative method, called “cryofixation”, to prevent brain shrinkage during the preparation for electron microscopy. The method, whose roots go back to 1965, uses jets of liquid nitrogen to “snap-freeze” brain tissue down to -90oC, within milliseconds. The brain tissue here was mouse cerebral cortex.