Shedding light on how the brain works
November 23rd 2009 22:24
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By Carolyn Y. Johnson Boston.com
More than two centuries ago, the Italian scientist Luigi Galvani found that electricity could make a dead frog’s leg kick, as if it were alive. Today, using the same basic principle but new tools, scientists are employing light to trigger brain cells - looking not for a kick, but for the origins of emotions, behaviors, and diseases in the brain.
Advanced imaging technologies have given neuroscientists new ways to peer into the working mind, but a precise understanding of how 100 billion brain cells create everything from memories to mental illness has remained elusive.
Now, by using gene therapy to insert light-sensitive proteins from algae and other organisms into brain cells, scientists are able to control specific brain circuits with light, and then watch what happens.
It’s a big shift, said Dr. Karl Deisseroth, a neuroscientist and psychiatrist at Stanford University, who compares the difference between imaging the brain and triggering individual cells to learning the rules of football by watching the game on a high-end TV or by controlling players.
“It wouldn’t matter how good your video camera was or your TV was; it would still be very mysterious, and that’s imaging,’’ Deisseroth said. The new technology, on the other hand, “allows you to play the role of coach and understand things.’’
Scientists start with algae, ancient forms of bacteria, and other organisms that contain proteins sensitive to light. They isolate the genes containing the instructions for making those proteins, insert the genes into a virus, and “infect’’ specific brain cells with the virus. The brain cells then start making the light-sensitive protein - essentially creating a switch that can turn a cell on or off when exposed to light. That’s earned the field the name optogenetics.
Scientists were not sure what to expect when they first did the experiment in mice. There were three possibilities when they flipped on the light: Nothing would happen, the animals might have seizures or other problems, or they would start seeing a measurable behavior.
But it worked. When the researchers threaded a fiber-optic cable into the brain of one of these mice and flashed a blue light, the animal ran in a circle. Other researchers found that fruit flies that had been genetically modified to carry a light-sensitive trigger in brain cells would jump up and fly away when they were hit with a laser beam.
Those experiments proved the concept would work, and the emerging field is now offering neuroscience the tantalizing possibility of being able to probe things like emotion and disease in a systematic way, said Ed Boyden, head of the synthetic neurobiology group at the Massachusetts Institute of Technology Media Lab.
“Typically in neuroscience, most of us focus on one region or pathway or one circuit or one part of the brain,’’ Boyden said. “But except for fairly slow imaging technologies, we can’t get a global picture of the brain yet - we can’t see how the whole thing works.’’ Optogenetics, he added, raises the prospect of mapping the brain.
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