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Noninvasive brain control may lead to new treatments

New light-sensitive protein found by MIT scientists

Jo Carlowe

Monday, 30 June 2014

Engineers from Massachusetts institute of Technology (MIT) have developed the first light-sensitive molecule that enables neurons to be silenced noninvasively, using a light source outside the skull.

This noninvasive approach could pave the way to using optogenetics (the use of light-sensitive proteins to suppress or stimulate electrical signals within cells) in human patients to treat conditions such as epilepsy and eye conditions.

Led by Ed Boyden, an associate professor of biological engineering and brain and cognitive sciences at MIT, the researchers described the protein, known as Jaws, in Nature Method*.

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 to be useful in controlling neuron activity.

Graduate student Amy 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: Jaws, retained its red-light sensitivity and had a stronger enough photocurrent to shut down neural activity.

Using this opsin, the researchers were able to shut down neuronal activity in a mouse brain with a light source outside the animal's head. The suppression occurred as deep as 3 millimetres in the brain.

Working with researchers at the Friedrich Miescher Institute for Biomedical Research in Switzerland, the MIT team also tested Jaws's ability to restore the light sensitivity of retinal cells in people with retinitis pigmentosa.

Friedrich Miescher, Institute scientists Botond Roska and Volker Busskamp have previously shown that some vision can be restored in mice by engineering those cone cells to express light-sensitive proteins. In the new paper, the scientists tested Jaws protein in the mouse retina and found that it more closely resembled the eye's natural opsins and offered a greater range of light sensitivity, making it potentially more useful for treating retinitis pigmentosa.

This type of noninvasive approach to optogenetics could also represent a step toward developing optogenetic treatments for diseases such as epilepsy, which could be controlled by shutting off misfiring neurons that cause seizures, Boyden says. 

However, he said more research is needed.

"Since these molecules come from species other than humans, many studies must be done to evaluate their safety and efficacy in the context of treatment.”

* Daniel R Hochbaum, et al. All-optical electrophysiology in mammalian neurons using engineered microbial rhodopsins. Nature Methods (2014) doi:10.1038/nmeth.3000

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