TIGHT SQUEEZE: Chemical fixation compacts synapses in a mouse brain (left), compared to freezing, which maintains the extracellular space (blue; right).GRAHAM KNOTT The paper
N. Korogod et al., “Ultrastructural analysis of adult mouse neocortex comparing aldehyde perfusion with cryo fixation,” eLife, 4:e05793, 2015.

The fix
Soaking brain tissue with chemical fixatives has been the go-to method of preserving specimens for decades. Yet few neuroscientists take into account the physical distortion that these chemicals cause. And even among those who do pay attention, “we don’t really know in quantitative terms how much really changes,” says Graham Knott, a morphologist at the École Polytechnique Fédérale de Lausanne in Switzerland.

Comparing fresh to fixed tissue, Knott and his colleagues found that chemical fixation shrank the tissue by 30 percent. “It raises the question of, ‘What on earth is going on if it shrinks that much?’” says...

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