OptoGenetics: Using Light to Control the Activity of the Brain

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Optogenetics earns Stanford professor Karl Deisseroth Keio Prize in Medicine

An idea that started as a long shot – using light to control the activity of the brain — has earned Karl Deisseroth the Keio prize in medicine. The technique, called optogenetics, is now widely used at Stanford and worldwide to understand the brain’s wiring and to unravel behavior. Many researchers expect it will lead to medical discoveries.

By Amy Adams

Today optogenetics is a widely accepted technology for probing the inner workings of the brain, but a decade ago it was the source of some anxiety for then assistant professor of bioengineering Karl Deisseroth.

Deisseroth had sunk most of the funds he’d been given to start his lab at Stanford into a crazy idea — that with a little help from proteins found in pond scum he could turn neurons on and off in living animals, using light. If it didn’t work he’d be out of funds with no published research, and likely looking for a new job.

Luckily, it worked, and has just earned Deisseroth, now the D. H. Chen Professor of bioengineering and of psychiatry and behavioral science, the 2014 Keio Medical Science Prize. Thousands of labs around the world are now using optogenetics to understand and develop treatments for diseases of the brain and mental health conditions and to better understand the complex wiring of our brains.

Deisseroth described the first step of his success in a seminal paper in 2005, but it was many years and many more academic papers before he could breathe easy. “There was a period of several years when not everyone who tried optogenetics got it working,” Deisseroth said. “There were some people who were skeptical about how useful it would be, and rightly so because there were a number of problems we still had to solve.”

Scientists worldwide have now used optogenetics to probe addiction, depression, Parkinson’s disease, autism, pain, stroke and myriad other conditions.

“Optogenetics has revolutionized neuroscience,” says Rob Malenka, a professor of psychiatry and behavioral sciences. Malenka is Deisseroth’s former postdoctoral advisor and is now a frequent collaborator. “It has allowed neuroscientists to manipulate neural activity in a rigorous and sophisticated way and in a manner that was unimaginable 15-20 years ago.”

Deisseroth adds, “I thought it would work but wasn’t sure it would quite reach this point.”

Many years before Deisseroth began tinkering with optogenetics, Francis Crick — the Nobel Prize winner who co-identified the structure of DNA — had argued that neuroscience needed a tool to control one type of cell in the brain while leaving the others unaltered. Such a tool, he said, would give neuroscientists a way of turning particular groups of neurons on and off to learn more about how the brain functions.

Decades later, scientists around the world were still discussing possible ways of carrying out that vision, including some approaches using light. Deisseroth decided to build his lab’s approach around proteins called microbial opsins that are found in single-celled organisms. He began with an opsin from green algae (aka pond scum) called channelrhodopsin, discovered by the German scientist Peter Hegemann.

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