Mining nature's diversity
To find a better alternative, Boyden, graduate student Amy Chuong, and colleagues turned to the natural world. Many microbes and other organisms use opsins to detect light and react to their environment.
Most of the natural opsins now used for optogenetics respond best to blue or green light.
Boyden's team had previously identified two light-sensitive chloride ion pumps that respond to red light, which can penetrate deeper into living tissue. However, these molecules, found in the bacteria Haloarcula marismortui and Haloarcula vallismortis, did not induce a strong enough photocurrent -- an electric current in response to light -- to be useful in controlling neuron activity.
Chuong set out to improve the photocurrent by looking for relatives of these proteins and testing their electrical activity. She then engineered one of these relatives by making many different mutants. The result of this screen,
Jaws, retained its red-light sensitivity but had a much stronger photocurrent -- enough to shut down neural activity.
"This exemplifies how the genomic diversity of the natural world can yield powerful reagents that can be of use in biology and neuroscience," says Boyden, who is a member of MIT's Media Lab and the McGovern Institute for Brain Research.
Using this opsin, the researchers were able to shut down neuronal activity in the mouse brain with a light source outside the animal's head. The suppression occurred
as deep as 3 millimeters in the brain, and was just as effective as that of existing silencers that rely on other colors of light delivered via conventional invasive illumination.
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