Genetically engineered protein responds remotely to red light.
A team of biological engineers has developed a light-sensitive protein that permits scientists to control activity inside the brains of mice from outside the rodents’ skulls. The protein, called Jaws, promises to expand scientists’ ability to study brain activity in experimental animals and -- eventually -- humans. Ultimately, it holds the prospect of facilitating treatment of human conditions such as epilepsy.
Researchers are also using the protein to treat eye disease in experimental animals. Here, an immediate goal is therapy for certain eye ailments in humans.
Scientists use optogenetics, as the technology is known, to study the behavior and pathology of experimental animals’ brains by shining light on proteins known as opsins. Introduced into the brain aboard viruses, the opsins respond to the light by suppressing or stimulating electrical signals in brain cells. Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. The red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light–induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice.
The opsins normally used in brain studies are sensitive to blue, green, or yellow light. Because bodily tissue absorbs those colors easily, the sources of such light must lie inside the brain. Typically, the light is delivered through an optical fiber implanted in an experimental animal’s brain. Jaws can noninvasively mediate transcranial optical inhibition of neurons deep in the brains of awake mice. The noninvasive optogenetic inhibition opened up by Jaws enables a variety of important neuroscience experiments and offers a powerful general-use chloride pump for basic and applied neuroscience.
A team led by Ed Boyden, associate professor of biological engineering and brain and cognitive sciences at the Massachusetts Institute of Technology, in Cambridge, reporting in Nature Neuroscience, demonstrated that red light shone from outside a mouse’s head can influence the Jaws protein up to three millimeters deep inside the brain. In fact, Boyden said, "we think the light goes further into the brain." A mouse’s brain is only about four millimeters thick.
"This is a huge advance, in that it allows for much deeper penetration of effective light," said David Lyon, an associate professor of anatomy and neurobiology at the University of California, Irvine School of Medicine. Lyon was not involved in the research on Jaws.