Red and blue lights flash, and a machine whirs like a distant swarm of bees. In a cubicle-sized room, Yoav Adam captures something no one has ever seen before: neurons flashing in real time, in a walking, living creature.
For decades scientists have been searching for a way to watch a live broadcast of the brain. Though neurons send and receive massive amounts of information (Toe itches! Fire hot! Garbage smells!) at speeds of up to 270 miles an hour, the brain’s electricity is invisible.
“You can’t see the electricity flowing through the neurons any more than you can see the electricity in a telephone wire,” said Adam Cohen, professor of chemistry and chemical biology and of physics at Harvard. So, to observe how neurons turn information (toe itches) into thoughts (“itching powder”), behaviors (scratching), and emotions (annoyance), we need to change the way we see.
In a new study published in Nature, Cohen does just that.
With first author and postdoctoral scholar Yoav Adam and a multi-institutional, cross-disciplinary research team, Cohen sheds literal light on the brain, transforming neural signals into sparks visible through a microscope.
Those sparks come from a protein called archaerhodopsin. When illuminated with red light, the protein can turn voltage into fluorescence (this and similar tools are known as genetically encoded voltage indicators, or GEVIs). Like an ultrasensitive voltmeter or the hair on your arm, archaerhodopsin changes form when it gets a jolt.
The Cohen team paired this with a similar protein that, when illuminated with blue light, causes neurons to fire. “This way,” Adam said, “we can both control the activity of the cells and record the activity of the cells.” Blue light controls; red light records.
The protein pair worked well in neurons outside the brain, in a dish. “But,” Cohen said, “the Holy Grail was to get this to work in live mice that are actually doing something.”
They finally found their grail after five years of intense collaboration between 24 neuroscientists, molecular biologists, biochemists, physicists, computer scientists, and statisticians. First, they tweaked the protein to work in live animals; then, with some adept genetic manipulation, they positioned the protein in the right part of the right cells in the mouse brain. Finally, they built a new microscope, customized with a video projector to shine a pattern of red and blue light into the live mouse’s brain, and onto specific cells of interest.
“You basically make a little movie,” Cohen said.
With red and blue light patterned on the brain, Adam can control which neurons fire when and can capture their electric activity as light. To identify individual neural signals in the bright chaos, the team designed one final tool: a software program that can extract specific neural sparks, like finding individual fireflies in a swarm.
