Researchers have exerted a little mind control over fruit flies by installing genetic “remote controls” within the insects’ brains. These controls, which make the insects respond to an external flash of ultraviolet light, provide a way for researchers to investigate how nerve cells work and interact without poking around in the flies’ brains.
Traditionally, scientists have studied the actions of nerve cells, or neurons, by stimulating them with implanted electrodes. The way in which animals, including people, respond during the stimulation can give researchers a sense of what role the neurons normally perform.
Implanted electrodes have several drawbacks. First, each electrode makes contact with only a few neurons at once, yet scientists aren’t always sure which neurons are being stimulated. Additionally, to prevent electrodes from dislodging, researchers must often sedate or restrain animals—actions that can change an animal’s behavior.
Seeking a way to avoid these problems, Gero Miesenböck and Susana Q. Lima of Yale University developed a new experimental system using the fruit fly. The scientists focused on a well-studied group of neurons in the flies known as the giant-fiber system, which is involved in the behavior of evading predators.
By genetically engineering the flies to express a particular membrane channel in their neurons, the researchers were able to install the equivalent of a remote control into the insects’ brains. The channel, called P2X2, transmits charged calcium and sodium atoms across cell membranes, causing the giant-fiber neurons to fire. Each channel opens its gates only after a molecule called adenosine triphosphate (ATP) binds to a receptor on the channel.
To remotely control the channels’ opening, Miesenböck and Lima developed molecules made up of ATP surrounded by a chemical cage that breaks down in the presence of ultraviolet light.
After injecting flies with a dose of the caged ATP, the researchers shined millisecond pulses of ultraviolet light on the insects. With each pulse, many of the chemical cages released their ATP captives, resulting in channels opening and neurons firing. As if on command, the flies began a series of escape movements—extending their legs, jumping, and beating their wings.
Unlike people, flies can see ultraviolet light. To make sure the flies’ escape response wasn’t activated just by seeing the light flashes, Miesenböck and Lima tested the same experiments on flies genetically engineered to be blind and even on decapitated flies. Both groups had responses similar to those of the sighted insects. Miesenböck and Lima report these findings in the April 8 Cell.
Ron Davis of Baylor College of Medicine in Houston calls the new technique “pretty clever.” Since each insect must be injected individually with caged ATP, he says that this method wouldn’t be practical for use in his own research, which includes work that uses thousands of fruit flies in experiments on the sense of smell and learning. Scientists who study behaviors such as courtship and aggression, and employ fewer flies, might find the technique more useful, Davis notes.
Although such mind control “has a little Frankenstein element in it,” Miesenböck predicts this noninvasive technique will eventually be used on people to study specific neurons’ functions.