Light-activated neurons hold bright promise for brain science
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When Edward Boyden was helping develop a tool to turn neurons on and off with light at Stanford a decade ago, he had a strong feeling it would spread far and wide. Even so, he’s been surprised by how quickly its fame has come.

“What I hadn’t quite anticipated was how fast it would take off,” said Boyden, who now leads the MIT Media Lab’s synthetic neurobiology research group. “It was almost as if the field was ready for the technology.”

It certainly was. On Sunday, Boyden and Stanford neuroscientist Dr. Karl Deisseroth, whose lab Boyden worked in, each received $3 million Breakthrough Prizes for their work on optogenetics.

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Scientists around the world have embraced the technology and are using it to study everything from behavior to learning to brain disease. This work has mostly been in rodent models, but now, for the first time, a clinical trial will use optogenetics to try to treat a genetic form of blindness.

“There are just huge frontiers out there for which optogenetics will be one of our most powerful tools,” said Robert Desimone, the director of the McGovern Institute for Brain Research at MIT.

Optogenetics makes living neurons sensitive to light by introducing special genes, carried by a virus, which produce photoreceptive proteins. By shining light on those cells — generally with a fiber-optic wire — scientists can either activate or suppress particular groups of neurons, exploring how different parts of the brain work and how they communicate with the rest of the brain.

A neuron expressing the protein channelrhodopsin is activated by light.
McGovern Institute for Brain Research at MITA neuron expressing a light-sensitive protein is activated by a beam of light.

The precision of the technique untangles the billions of cells swarming in the brain, pinpointing, for example, what circuits influence anxiety or thirst. Scientists can investigate previously untestable hypotheses, discovering what happens when certain pathways are ramped up or shut down.

“The idea that we could perturb these individual elements, these individual cell types and circuits, is something we’ve long needed,” said Anatol Kreitzer, an associate investigator at the Gladstone Institutes in San Francisco.

The huge range of studies underway reflects the usefulness of optogenetics. Researchers at the University of California, Irvine, for example, have halted epileptic seizures in mice with the help of the technique. Kreitzer has studied how motor problems associated with Parkinson’s disease, also in mice, arise from a brain region called the basal ganglia. And scientists at the Allen Institute for Brain Science in Seattle are studying how various cells in mice affect various behaviors, including arousal, attention, and visual processing.

“By silencing certain visual areas with optogenetics, we can ask whether these areas are important in a visual task,” said Jack Waters, an associate investigator there.

Matt Carter, an assistant biology professor at Williams College, is trying to learn more about the parts of the brain that control hunger and fullness. He’s curious about what happens, for example, if both appetite and appetite suppression are stimulated. “What’s the degree to which the hunger area overcomes that, or vice versa?” Carter said.

Research efforts have honed the technology’s precision and power over the years, and now, it is moving out of the lab and into clinical trials. This month, RetroSense Therapeutics — one of a number of companies studying optogenetics as a potential therapy — started recruiting patients with the genetic disease retinitis pigmentosa for a 15-person clinical trial. The trial aims to see if optogenetics is safe to use in people blinded by the disease or those whose vision has been severely damaged.

Retinitis pigmentosa kills the photoreceptor cells in the retina known as the rods and cones, but leaves untouched other cells that send signals to the brain. In the trial, those secondary cells will be made light-sensitive via an injection in the eye. The idea is that those cells can then become stand-ins for the lost photoreceptors.

The first phase of the trial is focused on assessing safety, but Sean Ainsworth, CEO of the Michigan-based RetroSense, said the company is also hoping to get some sense of what level of vision can be restored. RetroSense licensed technology from Wayne State University to develop its therapy.

By focusing on the eye, RetroSense’s approach avoids having to find a way to get a light into a patient’s brain to incite a reaction. (Mouse studies still require surgical procedures to implant the fiber-optic wire.) But some researchers think one day a wireless light source could be similarly inserted in the human brain to treat patients with psychological or psychiatric disorders.

Boyden, meanwhile, continues to use optogenetics. He has been working on a project looking at how different colors of light can best control neuronal circuits, and he hopes improvements in the technology could eventually help scientists control single neurons. He’s also interested in creating better maps of the entire brain, a task that has captivated neuroscientists in recent years and, for Boyden, could connect back to his passion for optogenetics.

“It’s very hard to perturb those cells if you don’t know where they are,” he said.

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