Window installed into a live brain

For the first time, we can peer through a glass window into a live brain and see the individual neurons up close.

What if we had a glass window into the brain that lets us look inside? For the first time ever, a team of physicists, chemists and biologists has done just that. Led by a microscopy pioneer, they peered into a living mouse's brain using powerful technology.

"You can look into the brain and see a true neuron in action," said physicist Stefan Hell, who leads the Max Planck Institute of Biophysical Chemistry's Department of NanoBiophotonics. His team's achievement is described in the latest issue of the journal Science.

Hell is well-known in the field for inventing a super-resolution "stimulated emission depletion" or STED microscope in the 1990s that can distinguish among features in living samples on a scale so small that general wisdom said it would be impossible.

With that microscope, Hell and his colleagues at Max Planck can discern features down to 70 nanometers in the living brain -- four times beyond what had been the physical limit.

An electron microscope can show powerful levels of detail, but only on dead cells mounted and prepared just so. Recently Hell's team took a live mouse that had been genetically modified so its neurons produce a fluorescent agent. They placed the mouse under anesthesia, opened its skull, and replaced part of the bone with a glass window.

Then, the STED microscope lens was attached to the window so light could be focused on an upper layer of the live mouse's brain. Operating almost like an ultra-precise spotlight, the microscope only illuminated individual neurons carrying the fluorescent marker. All the other cells were dark, letting the neurons shine. (The mouse survived the procedure.)

The resulting images from the live brain have an unprecedented level of clarity, Hell said. Little protrusions with thin necks and a cup-like shape at the end can be seen on the neurons. These "dendritic spines" are the input, the place where a neuron receives signals from a synapse.

Since their technique requires a transgenic animal whose neurons fluoresce, Hell said the plan isn't to make such a window for any human brains. However, there is potential to use this approach for research into treating or even preventing certain neurological diseases.

"I think we can learn a lot about what's going wrong, for example, at a synapse in certain cases," Hell said. "That door is now slammed wide open because one can access a level of functionality, a level of detail that is really critical."

Next, Hell said he and his colleagues want to help neuroscientists use their method to learn about brain functions that are still poorly understood. They would also like scientists to advance research into potential treatments by studying malfunctioning synapses in live animal brains. As physicists, he added, his team will work on producing sharper images.

From Discovery News