Using the STED microscopy developed by Stefan Hell, researchers at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany have, for the first time, managed to record detailed live images inside the brain of a living mouse. Captured in the previously impossible resolution of less than 70 nanometers, these images have made the minute structures visible which allow nerve cells to communicate with each other. This application of STED microscopy opens up numerous new possibilities for neuroscientists to decode fundamental processes in the brain.
STED microscopy has already found wide application in fields ranging from materials research to cell biology. Under this microscope, cell cultures and histological preparations have offered unique insights into the cellular nanocosmos. The first real-time video clips from the interior of a nerve cell have demonstrated how tiny transmitter vesicles migrate within the long nerve cell endings.
A Vision Becomes Reality
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.