Silencing Epilepsy With A Flash of Light

Traditionally, scientists and doctors have sent messages to our brain cells in one of two ways: electrically (via electrodes or chips implanted in the brain) or chemically (hello Xanax, Zoloft, and Ativan). But one of the hottest new fields in science is optogenetics, in which scientists engineer neurons to fire in response to flashes of light.

This improbable and astonishing development makes use of specialized proteins called opsins, which are naturally present in plants, fungi, and bacteria and allow these organisms to respond to light. (Opsins are also present in animal eyes, but optogeneticists tend to use forms of the proteins that are derived from “simpler” lifeforms.) Scientists can take the genes that code for these opsins and inject them directly into the brain, where some neurons will take the foreign DNA segments up into their own genomes. The nerve cells will then start churning out opsins.

Once inside a neuron, opsins work as light-activated channels, regulating the flow of electrically charged particles, or ions, into the cell. Hit the neuron with light, and the channel will open; ions will flow into the cell and change the voltage inside. There are many different kinds of opsins, and they have varied effects–some allow positively charged ions into the neuron and trigger the cell to fire. Others grant entry to negatively charged ions, making a neuron less likely to fire.

By modifying different kinds of neurons to express different types of opsins, scientists can make living brains selectively responsive to light–shine a blue light on the brain, for instance, and some neurons will start firing away. Shine an orange light on the brain and other neurons will go silent.

The technique has great promise for basic research. By turning a specific group of neurons on and off–and then watching how an animal responds–scientists can begin to unravel the precise roles that certain neural circuits and brain regions play in a variety of behaviors.

But there’s also been a tremendous amount of excitement about the possibility that optogenetics may open up new treatment options for a variety of neurological disorders. Scientists have dreamed of so-called “optical” prostheses: tiny arrays of lights that could be implanted into the brain and used to flip the switch on specific neural circuits involved in diseases ranging from epilepsy to Parkinson’s.

A new study in Nature Communications brings us one significant step closer to this dream. A team of neuroscientists from the University of California, Irvine managed to stop mouse seizures in their tracks using mere flashes of light.

The researchers threaded thin fiber optic cables into the brains of genetically modified, epilepsy-prone mice. The rodents had been engineered to express one particular opsin–known as halorhodopsin–in some of their neurons. Halorhodopsin is an inhibitory opsin; when activated by yellow light, it allows negatively charged ions into neurons, making them less likely to fire.

The scientists also connected the mice to an EEG machine, which measured the electrical activity in the rodents’ brains, and developed software that could recognize the EEG patterns that accompanied seizures. At the first sign of a seizure, the software triggered the fiber optic cable to deliver pulses of light directly into the animals’ brains.

The light activated the opsins and silenced the overexcited neurons, rapidly stopping the seizures; 57 percent of seizures ceased within a single second. (Flashes of light also reduced the length of seizures by an average of 70 percent.)

Of course, this paper is just one small study of epileptic mice, but it represents  an exciting step toward the development of optical neural prostheses.

Reference: Krook-Magnuson E, Armstrong C, Oijala M, & Soltesz I (2013). On-demand optogenetic control of spontaneous seizures in temporal lobe epilepsy. Nature Communications 4 PMID: 23340416

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