Optogenetics Probes Create Their Own Light

A novel class of proteins that create their own light could improve the versatility, scalability and practicality of optogenetics.

Researchers at Emory University and the Georgia Institute of Technology have developed inhibitory luminopsins (short for luminescent opsins) as an alternative method to deliver the light required to activate opsins, or engineered light-sensitive proteins. The introduction of opsins into animal brains and their subsequent stimulation or silencing results in behavioral changes. The luminopsins inhibit neuronal activity both in response to light and to a chemical supplied externally.

Bioluminescence from cells cultured in a multielectrode array, next to a fiber optic cable. Courtesy of Jack Tung.

In conventional optogenetics, fiber optic cables deliver light to regions in the brain; such cables have a limited reach, pose a risk of infection and can limit animals' movements.

To supply light locally and internally, the researchers took the enzyme luciferase from the soft coral Renilla, which glows in the presence of its substrate luciferin, and fused it to an inhibitory opsin. The resulting fusion protein is the first reported excitatory luminopsin to be demonstrated in live animals, the researchers said.

The researchers injected a gene vector encoding the luminopsins into the globus pallidus — an area of the brain involved in motor control — on one side of the brains of rats. Two weeks later, the rats were injected with luciferin, which had the effect of disabling the globus pallidus. In response to the drug amphetamine, the animals rotated preferentially in one direction, mimicking behavior that results from damage to one side of the globus pallidus.

"We think that this approach may be particularly useful for modeling treatments for generalized seizures and seizures that involve multiple areas of the brain," said biomedical engineering doctoral student Jack Tung. "We're also working on making luminopsins responsive to seizure activity: turning on the light only when it is needed, in a closed-loop, feedback-controlled fashion.”

The researchers also showed that luminopsins and luciferase together could suppress neural activity in the hippocampus of anaesthetized rats.

The research was published in Scientific Reports (doi: 10.1038/srep14366).