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Imagine using a remote control to command a living thing. Researchers have done just that, controlling fruit flies with a laser. As this ScienCentral News video explains, the research could lead to ways to control behaviors like overeating.
Remote-controlled Flies
Making creatures do what we want at the flick of a switch sounds more like Frankenstein than real science, but scientists have discovered that using a laser, they can make headless fruit flies (Drosophila melanogaster) jump, flap their wings and fly on command.
But Yale University neurologist Gero Miesenboeck and his team weren't out just to create remote-controlled insects. They hoped to study nerve-cell activity and connections, and learn how nerve cell circuits process information related to specific behaviors — from simple movements to more complex behaviors like learning, aggression and even abstract thoughts, like how they understand notions of punishment and reward. "The nervous system is simple enough to raise hopes that we can actually some day understand how it works and yet it's complex enough to produce really, really interesting behaviors," Miesenboeck says. "Now it is possible to control specific groups of nerve cells."
He says controlling specific nerve cells (neurons) may reveal what's behind behaviors that some of us want to stop. — matching specific cells to behaviors, scientists may one day be able to use optics like this to create drugs that target undesirable behavior, such as overeating.
"The clinical value of the approach that we have invented lies there, to associate specific types of nerve cells in the brain firmly with the expression of specific behaviors," Miesenboeck explains.
Illuminating headless flies with laser light.
As reported in Discover magazine, the team used flashes of harmless laser light to test a group of nerve cells in flies that trigger a natural escape response.
Normally, when the escape response is triggered, the brain sends a signal down to the thoracicganglion (like a human spinal cord), which in turn signals the muscles, and that initiates jumping and flapping. "We focused on a very simple and very well understood neural circuit in the brain of the fly that controls its escape behaviors," Miesenboeck says. "If you've ever tried to swat a fly you've worked with this circuit. It's the circuit that's normally triggered by the casting of a shadow. So whenever you move your hand over a fly that you try to swat, you may have noticed that the fly typically, as soon as the shadow moves over, it jumps into the air and flies away. And that's because you trigger that circuit."
But when they cut off the heads, the flies lack the normal input circuit from the brain and stop moving. In this case the flies were genetically altered with "photo-triggers" that recognize the outside signal of the laser light pulse and translate that signal into the electrical signals of nerve-cell activity to produce the escape response when certain nerve cells are lit up with a laser.
"We had to express these different photo-triggers in different nerve cells in the nervous system, and then make sure that once we shone light on the flies, we also activated the neurons that we wanted to activate and to activate them selectively," he explains.
Activating this circuit on command in headless flies, which can live up to a day if kept moist, Miesenboeck showed he could control the flies' escape behavior, but, he says the technique could be used to look at just about any array of nerve cells in the brain. "There's essentially no practical limit on the number of nerve cells that one can address in parallel. These nerve cells do not have to be in any precise spatial relationship with each other, they can be scattered throughout the brain — as some of the cells that we have studied in the brains of our fruit flies were — and you can still reach them all," he says. "As long as the photo-trigger is encoded genetically, as it is in our case, it has a built-in selectivity for only certain classes of neurons — neurons that have a particular genetic makeup."
Until now researchers could only manipulate neurons directly and invasively by stimulating them with electrode. "[The electrode] goes back more than 200 years to [Luigi] Galvani who used electrodes to make frogs' legs twitch, and it has a really distinguished history of discovery," says Miesenboeck. "But… electrodes are very, very cumbersome to use… it's very, very diff to conduct experiments in freely moving animals with electrodes."
While the researchers' first study showed how to manipulate a behavior the flies need, Miesenboeck says the technique can be used to discover other nerve cells in flies that may close the curtain on behaviors we can do without.
"If you had an animal in which you found a cell in the brain that when stimulated leads to massive eating, I think that would be a rather interesting target for attempts to control food intake, obesity, weight loss and so forth," he says. "Once you know of such a link, you know where you can intervene, and that intervention, in all likelihood, will still be through conventional drug therapy rather than through optical stimulation. But the approach of optical stimulation tells you where your drugs should be acting."
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