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Monday, March 12, 2007 TR10: Neuron ControlKarl Deisseroth's genetically engineered "light switch," which lets scientists turn selected parts of the brain on and off, may help improve treatments for depression and other disorders. By Emily Singer
This article is one in a series of 10 stories we're running this week covering today's most significant emerging technologies. It's part of our annual "10 Emerging Technologies" report, which appears in the March/April print issue of Technology Review. In his psychiatry practice at the Stanford Medical Center, Karl Deisseroth sometimes treats patients who are so severely depressed that they can't walk, talk, or eat. Intensive treatments, such as electroconvulsive therapy, can literally save such patients' lives, but often at the cost of memory loss, headaches, and other serious side effects. Deisseroth, who is both a physician and a bioengineer, thinks he has a better way: an elegant new method for controlling neural cells with flashes of light. The technology could one day lead to precisely targeted treatments for psychiatric and neurological disorders; that precision could mean greater effectiveness and fewer side effects. While scientists know something about the chemical imbalances underlying depression, it's still unclear exactly which cells, or networks of cells, are responsible for it. In order to identify the circuits involved in such diseases, scientists must be able to turn neurons on and off. Standard methods, such as electrodes that activate neurons with jolts of electricity, are not precise enough for this task, so Deisseroth, postdoc Ed Boyden (now an assistant professor at MIT; see "Engineering the Brain"), and graduate student Feng Zhang developed a neural controller that can activate specific sets of neurons. They adapted a protein from a green alga to act as an "on switch" that neurons can be genetically engineered to produce (see "Artificially Firing Neurons," TR35, September/October 2006). When the neuron is exposed to light, the protein triggers electrical activity within the cell that spreads to the next neuron in the circuit. Researchers can thus use light to activate certain neurons and look for specific responses--a twitch of a muscle, increased energy, or a wave of activity in a different part of the brain. Deisseroth is using this genetic light switch to study the biological basis of depression. Working with a group of rats that show symptoms similar to those seen in depressed humans, researchers in his lab have inserted the switch into neurons in different brain areas implicated in depression. They then use an optical fiber to shine light onto those cells, looking for activity patterns that alleviate the symptoms. Deisseroth says the findings should help scientists develop better antidepressants: if they know exactly which cells to target, they can look for molecules or delivery systems that affect only those cells. "Prozac goes to all the circuits in the brain, rather than just the relevant ones," he says. "That's part of the reason it has so many side effects." In the last year, Deisseroth has sent his switch to more than 100 research labs. "Folks are applying it to all kinds of animals, including mice, worms, flies, and zebrafish," he says. Scientists are using this and similar switches to study everything from movement to addiction to appetite. "These technologies allow us to advance from observation to active intervention and control," says Gero Miesenböck, a neuroscientist at Yale University. By evoking sensations or movements directly, he says, "you can forge a much stronger connection between mental activity and behavior." Deisseroth hopes his technology will one day become not just a research tool but a treatment in itself, used alongside therapies that electrically stimulate large areas of the brain to treat depression or Parkinson's disease. By activating only specific neurons, a specially engineered light switch could limit those therapies' side effects. Of course, the researchers will need to solve some problems first: they'll need to find safe gene-therapy methods for delivering the switch to the target cells, as well as a way to shine light deep into the brain. "It's a long way off," says Deisseroth. "But the obstacles aren't insurmountable." In the meantime, neuroscientists have the use of a powerful new tool in their quest to uncover the secrets of the brain. |




Comments
gabrielg01 on 03/13/2007 at 1:20 AM
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I guess this is one of those cases when a scientist is so enamored with the project that he/she simply becomes blind to the bigger picture.
If we get to have a safe gene-therapy, which can be specifically targeted to certain neurons (this is close to sci-fi), then you could just use this gene technology to fix whatever was wrong with the neurons in the first place. There would be no more need for light switches.
This light switch is an important investigation technique in the lab. But don't hype it, and oversell it as some kind of cure.
davidmeissner on 03/17/2007 at 9:34 PM
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Also, there's a huge difference between knowing which general set of neurons is responsible for a condition, and knowing what the endogenous cause of that problem is. So it's certainly not the case that "you could just use this gene technology to fix whatever was wrong with the neurons in the first place."
I agree, it's hyped, but I think it's worthwhile that people are thinking about how these technologies might be applied.
karlhedderich on 03/14/2007 at 11:51 AM
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mike_s on 03/18/2007 at 10:31 PM
2