What was only an ambitious vision a year ago has now become reality: to also study higher living organisms at this sharp resolution in the nanometer range. By looking directly into the brains of living mice using a STED microscope, Hell and his team were the first ones to image nerve cells in the upper brain layer of the rodent with resolution far beyond the diffraction limit.
“With our STED microscope we can clearly see the very 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,” explains Hell. They are the clearest images of these fundamental contact sites in the brain to date. “To make these visible, we take genetically modified mice that produce large quantities of a yellow fluorescing protein in their nerve cells. This protein migrates into all the branches of the nerve cell, even into smallest, finest structures,” adds Katrin Willig, a postdoctoral researcher in Hell’s department. The genetically modified mice for these experiments originated from the group of Frank Kirchhoff at the Göttingen Max Planck Institute for Experimental Medicine. Images of the nerve cells taken seven to eight minutes apart revealed something surprising: The dendritic spine heads move and change their shape. “In the future, these super-sharp live images could even show how certain proteins are distributed at the contact points,” adds Hell. With such increasingly detailed images of structures in the brain, Hell’s team hopes to shed light onto the composition and function of the synapses on the molecular level.
Such insights could also help to better understand illnesses that are caused by synapse malfunction. Among these so-called synaptopathies are, for example, autism and epilepsy. As Hell explains, “Through STED microscopy and its application in living organisms, we should now be able to gain optical access of such illnesses on the molecular scale for the first time.” As one of the two representatives of the Göttingen Research Center Molecular Physiology of the Brain funded by the German Research Foundation, he is committed to collaboration in his further research. Together with neurobiologists and neurologists, he and his team plan to transfer the progress made in imaging technology into fundamental knowledge about the functioning of our brains.
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