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.