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2005

Shedding Light on Neurons With an Off-and-On Switch
The New York Times, April 12, 2005
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The 18th-century Italian anatomist Luigi Galvani found that a spark could make a frog's leg kick. His experiments established that electricity was the hidden force nerves used to control the body. Now researchers at Yale have done Galvani one better. They can make fruit flies walk, leap or fly by shining a laser at the insects, setting off certain neurons inside them.

It's possible, at least in theory, that this method could someday be developed into a sort of animal remote control. But its biggest promise is as a scientific tool that may shed light on the function of different kinds of neurons. The ability to switch on particular neurons may allow scientists to discover clues about a range of disorders, from Parkinson's disease to drug addiction.

Dr. Susana Lima and Dr. Gero Miesenböck, the authors of the study, engineered a light-sensitive trigger that could be attached to neurons of flies.

The researchers began their work by transplanting a gene related to the structure of certain pain-sensing neurons in rats. Dr. Lima and Dr. Miesenböck added genetic on-switches to the rat gene so that it would become active only in a particular type of neuron in a fly.

To turn the transplanted rat channels into light-sensitive triggers, Dr. Lima and Dr. Miesenböck then took advantage of the way the altered neurons produced electric impulses. Unlike fly neurons, the altered cells could produce electric impulses only in the presence of a molecule called ATP.

The researchers then injected ATP into the flies. But they used a ''caged'' form of the molecule that would not affect the neurons unless a flash of ultraviolet light released it.

Dr. Lima and Dr. Miesenböck carried out their first test with giant fiber neurons, which run down the length of a fly, and are responsible for the insect's escape response.

The researchers allowed the engineered flies to grow into adults and then decapitated them. Decapitated flies can survive a day or more without their heads, although they spend that time standing motionless. But when the flies were injected with ATP and then zapped with a laser for a fifth of a second, they jumped up and began flapping their wings in 60 to 80 percent of the trials.

''When we saw these headless bodies flying away, we were absolutely stunned,'' Dr. Miesenböck said. The researchers were later able to get healthy flies to fly as well.

''It just blows you away,'' said Dr. Ronald Davis, a neuroscientist at Baylor College of Medicine in Houston.

He considers the new method an important addition to the toolbox neuroscientists use to study the nervous system. ''We're always looking for ways to mimic a biological event,'' he said.

Dr. Davis and other neuroscientists use fruit flies as animal models for disorders of the nervous system. Drug addiction and Parkinson's disease, for example, are linked to an imbalance in the production of a neurotransmitter called dopamine.

Dr. Lima and Dr. Miesenböck were also able to engineer flies with the light switch attached only to dopamine-producing neurons. When they exposed these flies to a laser flash, the flies began to walk furiously in circles or crisscross the dish in which they are housed. The effects lasted for as long as two minutes after the flash.

The researchers published their results in the April 8 issue of the journal Cell.

Dr. Miesenböck hopes to use this new method to study the nervous system of flies and other animals, including mice. He acknowledges, however, that the same method might also be used to engineer animals that can be controlled remotely.

It was only after he and Dr. Lima submitted their results to Cell that Dr. Miesenböck learned about a prelude to his work, conducted in the 1960's by the Yale neurophysiologist Dr. José Delgado. On a flight to Los Angeles, Dr. Miesenböck read about how Dr. Delgado had implanted electrodes in the brain of a bull. He was able to stop it in midcharge by turning on the electrodes with radio waves.

The parallels were obvious. ''I almost fell out of my seat,'' Dr. Miesenböck said. ''It was a good thing I was locked in.''


Copyright 2005 The New York Times Company

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