New Technique Enables Nanoscale Images Inside Living Brain

STED image of a nerve cell in the upper brain layer of a living mouse (Max Planck Institute for Biophysical Chemistry)

Researchers at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany have developed a technique to record detailed live images inside the brain of a living mouse. The technology, called stimulated emission depletion (STED) fluorescence microscopy is described in the 3 February issue of the journal Science; paid subscription required.

The team led by Stefan Hell captured images of minute structures in nerve cells with a resolution of less than 70 nanometers (1 nanometer equals 1 billionth of a meter). With current optical microscopes structures located closer together than 200 nanometers appear as a single blurred spot.

With STED microscopy, closely-positioned elements are kept dark under a special laser beam so that they emit fluorescence sequentially, rather than all at once, which makes them easier individually to distinguish. The technique enabled Hell’s researchers to increase the imaging resolution as much as 10 times, compared to conventional microscopes.

The STED technology had a little help from the mice in order to make it work. The researchers used genetically modified mice that produced large quantities of a yellow fluorescing protein in their nerve cells, which migrated into all branches of those cells. Mice with these characteristics were developed at the neighboring Max Planck Institute for Experimental Medicine.

The results showed images of the fine dendritic structures of nerve cells at which the synapses are located in the brain of a living mouse. “At a resolution of 70 nanometers, we easily recognize these so-called dendritic spines with their mushroom- or button-shaped heads,” says Hell. “They are the clearest images of these fundamental contact sites in the brain to date.”

With more detailed images of structures in the brain, the team hopes to learn more about the composition and function of the synapses on the molecular level. These discoveries could better help understand illnesses that are caused by synapse malfunction, such as autism and epilepsy.

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