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Switching brain cells on and off using multicolored light


PALO ALTO, Calif. – Optogenetics – an emerging field of research that involves selectively switching brain cells on and off using flashes of light – could provide scientists with a better understanding of the abnormal brain activity associated with depression, Parkinson’s disease and more. To date, reliably activating brain cells has required blue light, but now researchers at Stanford University have found a way to use multiple visible colors of light, and even wavelengths at the infrared border, to inhibit cells.

“Optogenetics is the use of light to control genetically defined populations of cells. Determining the role of specific cell populations in the normal and diseased brain has been a long-sought goal of neuroscience,” said Dr. Viviana Gradinaru, who works in the optogenetics laboratory of professor Karl Deisseroth at the university. “Now, with optogenetics, it is possible to ask precise questions about different cell types in animal models of disease.”

Viviana Gradinaru is in the optogenetics laboratory of professor Karl Deisseroth at Stanford University. Images courtesy of Viviana Gradinaru and Karl Deisseroth.

Triggering cells

Optogenetics works by using a specially engineered virus to insert genes into cells to trigger the generation of light-sensitive proteins. With stimulation by light of a certain wavelength, cell activity can be either enhanced or suppressed. One of the most important advances the Stanford team described in the April 2, 2010, issue of Cell is the ability to use light bordering on infrared wavelengths to suppress cell activity.

Light in this regime can penetrate much deeper into living tissue, meaning that cells can be turned off in larger areas of the brain. This is crucial for producing not only more widespread and stronger effects in small animals but also meaningful effects in larger animals, such as primates. Compared with lower wavelengths, light at the infrared border also can deliver less energy to tissue, which may make it especially safe.

A device called an optrode is used for delivering light to the brain via a fiber optic coupled to a laser and for recording neuronal activity in vivo via an electrode. Blue light is used to activate neurons that express the light-sensitive protein channelrhodopsin.

“With the new generation of optogenetic inhibitors, especially eNpHR3.0, a range of visible wavelengths (from blue to red) can be used at safe low-light powers to silence neurons,” Gradinaru said. “Near-infrared inhibition is also possible, which is especially important for in vivo experiments since it allows greater accessibility to larger volumes of tissue.”

Meanwhile, being able to use any color to control cells also opens the door to performing more complex experiments, because different colors of light could be used at the same time. For example, blue light could be used to activate one kind of cell at the same time red light is used to shut off another kind, allowing the effects of this combination as well as others to be studied.

The researchers have already distributed their tools to many laboratories around the world that will apply the technique to targeting their own specific questions. This includes investigating various circuits such as motor control, as well as reward and addiction in many different species, including flies, worms, rodents and primates.

Closer to home, the Stanford group also plans to apply the research to instructing better therapies for psychiatric patients in its School of Medicine. In addition to using the tools to study animal models of neurological and psychiatric disorders, Deisseroth sees patients in the psychiatry clinic once a week. “We hope that our efforts and those of our collaborators with the application of optogenetics will lead to a better understanding of malfunctioning brain circuitry and in the long run educate better therapies,” Gradinaru said.

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