Pulsing Light Silences Overactive Neurons

[Bernard]

Scientists at the MIT Media Lab have invented a way to reversibly silence brain cells using pulses of yellow light, offering the prospect of controlling the haywire neuron activity that occurs in diseases such as epilepsy and Parkinson's disease.

...

Many epilepsy patients have implanted electrodes that periodically give their brains an electric jolt, acting as a defibrillator to shut down overactive neurons. This new research opens up the possibility of an optical implant that could do the same thing, using light instead of electricity. The Media Lab neuroengineering group plans to start studying such devices in transgenic mice this year.

The group also plans to use the new method to study neural circuits. Last year, Boyden devised a technique to stimulate neurons by shining blue light on them, so with blue and yellow light the researchers can now exert exquisite control over the stimulation and inhibition of individual neurons.

Learning more about the neural circuits involved in epilepsy could help scientists develop devices that can predict when a seizure is about to occur, allowing treatment (either shock or light) to be administered only when necessary, Boyden said.

Pulsing Light Silences Overactive Neurons

[RobinN]

Neuroscientists at MIT have developed a powerful new class of tools to reversibly shut down brain activity using different colors of light. When targeted to specific neurons, these tools could potentially lead to new treatments for the abnormal brain activity associated with disorders such as chronic pain, epilepsy, brain injury, and Parkinson's disease.

The tools work on the principle that such disorders might be best treated by silencing, rather than stimulating, brain activity. These "super silencers" exert exquisite control over the timing of the shutdown of overactive neural circuits – an effect that's impossible with existing drugs or other conventional therapies.

"Silencing different sets of neurons with different colors of light allows us to understand how they work together to implement brain functions," explains Ed Boyden, senior author of the study, to be published in the Jan. 7 issue of Nature. "Using these new tools, we can look at two neural pathways and study how they compute together. These tools will help us understand how to control neural circuits, leading to new understandings and treatments for brain disorders – some of the biggest unmet medical needs in the world." Boyden is the Benesse Career Development Professor in the MIT Media Lab and an associate member of the McGovern Institute for Brain Research at MIT.

Boyden's super silencers are developed from two genes found in different natural organisms such as bacteria and fungi. These genes, called Arch and Mac, encode for light-activated proteins that help the organisms make energy. When neurons are engineered to express Arch and Mac, researchers can inhibit their activity by shining light on them. Light activates the proteins, which lowers the voltage in the neurons and safely and effectively prevents them from firing. In this way, light can bathe the entire brain and selectively affect only those neurons sensitized to specific colors of light. Neurons engineered to express Arch are specifically silenced by yellow light, while those expressing Mac are silenced by blue light.

"In this way the brain can be programmed with different colors of light to identify and possibly correct the corrupted neural computations that lead to disease," explains co-author Brian Chow, postdoctoral associate in Boyden's lab.

In 2005, Boyden, in collaboration with investigators at Stanford University and the Max Planck Institute, introduced the first such "optogenetic" technique, so called because it combines the use of optics with gene delivery. The 2005 tool, now widely used, involves a light-activated ion channel, ChR2, which allows light to selectively turn on neurons in the brain.

Two years later, Boyden demonstrated that halorhodopsin, another light-sensitive protein, could inhibit the activity of neurons when illuminated. "But the genomic diversity of the world suggested that more powerful tools were out there waiting to be discovered," Boyden says. His group accordingly screened a diverse set of microbial light-sensitive proteins, and found the new multicolor silencers. The newly discovered tools are much better than the old. Arch-expressing neurons were switched off with greater precision and recovered faster than halorhodopsin-expressing neurons, allowing researchers to manipulate different neurons with different colors of light.

"Multicolor silencing dramatically increases the complexity with which you can study neural circuits," says co-author Xue Han, postdoctoral researcher in Boyden's lab. "We will use these tools to parse out the neural mechanisms of cognition."

How they did it: MIT researchers loaded the Arch and Mac genes into viruses that inserted their genetic cargo into mouse neurons. Optical fibers attached to lasers flashed light onto the neurons, and electrodes measured the resulting neural activity. [See graphic]

Next steps: Boyden's team recently demonstrated the efficacy of ChR2 in monkeys with no apparent side effects. Determining whether Arch and Mac are safe and effective in monkeys will be a critical next step toward the potential use of these optical silencing tools in humans. Boyden plans to use these super silencers to examine the neural circuits of cognition and emotion and to find targets in the brain that, when shut down, could relieve pain and treat epilepsy. His group continues to mine the natural world for new and even more powerful tools to manipulate brain cell activity – tools that, he hopes, will empower scientists to explore neural circuits in ways never before possible.

http://www.eurekalert.org/pub_releas...-mns010410.php

[epileric]

That would explain why yellow or blue tinted glasses seem to help some peoples seizures.

[Bernard]

I merged the new article with one posted almost two years ago about the same research. Looks like the future is bright.

[BuckeyeFan]

WOW!

I like the fact that they are incorporating the "also plans to use the new method to study neural circuits" into the program. This may lead in several other directions as well. Not just a test this trigger and measure the reaction. They want to know why.

WOW!

[Nakamova]

Sounds extremely promising! But my sci-fi/paranoid streak makes me worry about what might happen if this kind of stuff is misused, like shutting down neurons to make someone "docile".

[flinnigan]

Nakamova, You must have seen Clockwork Orange. Its OK only I think I'm funny according to my kids.

But this does sound interesting. MIT is an amazing place.

[Nakamova]

Yup, Clockwork Orange, Brazil, Twelve Monkeys, Bride Wars -- all those terrifying mind control movies. Wait, one of those movies is just terrible not terrifying...

[Rae1889]

So how would this work for some one (like myself) that is photosensitive to coloured lights flashing/pulsing? would this not make it worse? plus what about people who are completely or partially coloured blind? (my left eye is red/green colour blind from an accident that left a scar on the optical nerve and retina)

[occb]

Huh. I wonder what's at work for someone like my partner who loathes sunlight. From noon until four he hides away into artifical light, because sunlight makes him want to crawl out of his skin -- it's like his brain is going nuts. It makes daytime functioning very difficult for him.

[Rae1889]

I find I can sleep better when its daylight out side and my room is bright, than I can in the dark. In the dark, it feels like my eyes are already closed but my mind is still on trying to sleep. So time flies by so fast.

but during the daylight, I know that the sunlight is there just through my eyelids and it lets me sleep. not sure why though.
I think i might be afraid of the dark too. I have a HUGE fear of the earth ending while i'm sleeping. Death and/or semi-survivable armageddon scare me almost nightly. bit OCD with some things.

[Bernard]

So how would this work for some one (like myself) that is photosensitive to coloured lights flashing/pulsing? would this not make it worse? plus what about people who are completely or partially coloured blind? (my left eye is red/green colour blind from an accident that left a scar on the optical nerve and retina)

They are using optical fibers to bring the light directly into the brain (ie. surgery required).

[epileric]

Boyden's discovery, published in the journal Nature this week, is a powerful new tool for neuroscientists struggling to understand the complexity of the brain. With it, researchers will be able to probe how the circuitry of the brain works by silencing certain very specific areas or types of brain cells and studying the effects.

What's especially useful about the method is that it allows researchers to re-activate the brain regions instantaneously by simply turning off the light.

While early work will be done in animals, Boyden thinks that his discovery will also soon be used as a prosthetic device in humans. It could quickly, and temporarily, shut down overactive brain regions implicated in conditions like epilepsy and depression. An animal experiment funded by the U.S. Army is now looking into whether the method could be used to treat post-traumatic stress disorder.

http://www.ctv.ca/servlet/ArticleNew...09?hub=SciTech

[RobinN]

I found this article to be interesting, because maybe there is a real future in light therapy for seizure and migraine control.

January 11, 2010
The painful aversion to light that sends migraine sufferers into darkened rooms when their throbbing headaches start surprisingly also affects some blind people, Boston researchers report in a paper that describes a new light-sensitive pathway in the brain that is separate from visual perception.

Rami Burstein of Beth Israel Deaconess Medical Center led a team of researchers who studied 20 blind people who were longtime migraine sufferers. Six of them could not see light at all because their eyes or their optic nerves had been damaged or surgically removed. Light did not worsen their headaches. The 14 others could detect light, but degenerative eye diseases had left the light-sensitive rods and cones in their retinas unable to perceive images. For these people, light did intensify the pain of their migraines, leading the authors to conclude that light receptors in the eye apart from those used for vision were related to exacerbating migraines.

To test this idea, the researchers followed nerve signals in rats exposed to light during induced migraines. They found that within a second, light increased activity in parts of the brain that were firing during migraines. The signals traveled along a pathway from the retina to the brain that was separate from the rods and cones, consistent with what light-sensitive blind migraine sufferers experience.

BOTTOM LINE: Sensitivity to light during migraines originates in a different pathway than the ones used for forming images, a study of blind people and lab animals found.

CAUTIONS: There may be differences between how anesthetized mice and awake humans experience light-exacerbated migraines, and there may be more than one brain mechanism involved in the process.

WHAT’S NEXT: Burstein’s team has won a five-year grant to look for ways to block light sensitivity during migraines.

WHERE TO FIND IT: Nature Neuroscience, Jan. 10

Vitamin D linked to racial disparity in heart deaths
Black people die from heart disease and strokes at rates higher than white people, a persistent disparity researchers have sought to explain by studying biological and societal differences. A new study points to a potential role for vitamin D. While vitamin D deficiency is common among all races, black people are less able to absorb vitamin D from sunlight because of darker skin.
Researchers at the University of Rochester and the University of California-Davis analyzed the medical records of more than 15,000 adults who participated in a government-run health survey from 1988 through 1994. By the end of 2000, 933 had died of cardiovascular causes.

When the researchers sorted people into four groups based on their vitamin D levels at the start of the study, those who had the lowest levels were 40 percent more likely to have died of cardiovascular causes. Overall, black people were 38 percent more likely to have died than white people. But for black people who had higher vitamin D levels, the risk fell to 14 percent higher than white people. For black people with both higher vitamin D and higher income, the difference disappeared.

BOTTOM LINE: Lower levels of vitamin D in African-Americans may partially explain the higher risk of cardiovascular death in black people compared with white people in the United States.

CAUTIONS: A retrospective study like this one can’t prove cause and effect. Also, the ways vitamin D might affect cardiovascular disease are not well understood.

WHERE TO FIND IT: Annals of Family Medicine, January/February