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Noninvasive Brain Control via Jaws!



Mind control, we’ve seen several semi [see very] invasive ways to make it happen here from the Labs. Now those crazy scientists from MIT  have developed a technique that allows researchers to enable neurons to be silenced noninvasively, using a light source outside the skull. All using a protein known as Jaws.

Optogenetics [a technology that allows scientists to control brain activity by shining light on neurons] uses light-sensitive proteins that can suppress or stimulate electrical signals within cells. This technique is very invasive though because it requires a light source to be implanted in the brain, where it can reach the cells to be controlled.

This noninvasive approach could [hopefully] pave the way to using optogenetics in human patients to treat epilepsy and other neurological disorders. Of course much more testing and development is needed before we will see this become mainstream.

Optogenetics [which is a very new technique that was developed over the past 15 years] has become a common laboratory tool for shutting off or stimulating specific types of neurons in the brain, allowing neuroscientists to learn much more about their functions. The new field has helped science understand functions of the brain that were total mysteries to us not that long ago.

Of course the neurons to be studied must be genetically engineered to produce light-sensitive proteins [known as opsins] which are channels or pumps that influence electrical activity. This is done by controlling the flow of ions [charged particles the brain uses to pass messages] in or out of cells. Researchers then insert a light source, such as an optical fiber, directly into the brain to control the selected neurons.

There is, of course a whole lot of drawbacks to this sort of approach, the implants can be difficult to insert and can be incompatible with many kinds of experiments, such as studies of development, during which the brain changes size, or of neurodegenerative disorders, during which the implant can interact with brain physiology. It also is difficult to perform long-term studies of chronic diseases with these implants.

To find a better alternative, researchers turned to the natural world. Many microbes and other organisms use opsins to detect light and react to their environment, in fact most of the natural opsins now used for optogenetics respond best to blue or green light.

The 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.

With that starting point, researchers set out to improve the photocurrent by looking for relatives of these proteins and testing their electrical activity. They then engineered one of these relatives by making many different mutants. The result of this, the Jaws protein, retained its red-light sensitivity but had a much stronger photocurrent — enough to shut down neural activity.

Using this opsin [Jaws], the researchers were able to shut down neuronal activity in the mouse brain with a light source outside the animal’s head. The suppression even occurred as deep as 3 millimeters in the brain. Amazingly it was just as effective as existing silencers that rely on other colors of light delivered via conventional invasive optical illumination.

But that’s not all, 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 [also known as cones]. In people with a disease called retinitis pigmentosa, where cones slowly atrophy and eventually causing blindness.

Friedrich Miescher Institute scientists previously have shown that some vision can be restored in mice by engineering those cone cells to express light-sensitive proteins like the ones used in optogenetics. In the new paper, researchers tested the Jaws protein in the mouse retina. Incredibly they found that it more closely resembled the eye’s natural opsins and offered a greater range of light sensitivity. This means that it is 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. Keep in mind though that 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.

So what’s next for the team? They are planning on doing further testing with the Jaws opsin for other applications where it might be useful. They are also going to be looking for other new light sensitive proteins all while looking for new screening approaches to help speed up the development of those proteins.

Need more Jaws? You probably want the full study —here!

Kramer, R., Mourot, A., & Adesnik, H. (2013). Optogenetic pharmacology for control of native neuronal signaling proteins Nature Neuroscience, 16 (7), 816-823 DOI: 10.1038/nn.3424



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