In the 1780s, Italian scientist Luigi Galvani discovered he could stimulate frog muscle by applying electric shocks. Two hundred years later, Yale scientists have traded in electrodes for a remote control, utilizing a technique that is the changing the way neurobiologists experiment.

Two neurobiologists at the Yale School of Medicine, cell biology assistant professor Gero Miesenboeck and postgraduate associate Susana Lima, recently discovered how to control fly behavior by genetically engineering neurons to be triggered by light signals. The laser induced the flies to walk, leap or fly, depending on which neuron contained the rat gene, Miesenboeck said.

They started their study, published in the April 8 issue of Cell, by inserting into Drosophila fruit flies a rat gene coding for an ion channel and a “caged” type of ATP that releases energy only when hit by ultraviolet light. Once they flashed the laser on the neuron, Miesenbooeck said the ATP released its energy, which activated the ion channels and stimulated the fly neurons.

The experiment’s objective was to find a new interface to “talk” with neurons while the animal is behaving, Lima said. Such conversation would enable scientists to understand more about how the nervous system works, opening new doors in neuroscience, she said.

“I see it mostly as a discovery engine,” Miesenboeck said.

In the past, scientists have used electrodes to stimulate certain behaviors in animals, but he said this conventional approach forced scientists to trigger neurons by targeting those clustered in anatomical locations, limiting their ability to identify the interconnected neural networks spread throughout the nervous system. Miesenboeck said the electrodes placed in select locations made triggering actions that required unrestrained movement difficult.

While neuroscience has traditionally been an observational science, he said this novel method provides a “stronger way of experimenting.”

Miesenboeck said the new technique provides a better way of linking the activity of specific neurons with the expression of certain behaviors. The breakthrough will also further human understanding of the way neural circuitry works as a system possible, he said.

Further research stemming from the study may benefit the knowledge of the mammalian nervous system, cell biology professor Pietro De Camilli said.

“The fundamental mechanisms [of the fly and mammal] are highly similar,” he said. “If you prove that this methodology can be used in a fly, it can also be used in a mammalian brain.”

However, De Camilli said the technique must be modified to work in mammals because a laser cannot penetrate a mammalian skull. The transplanted sensor must be activated by chemicals, he said.

This new methodology promises immediate benefits in drug research, De Camilli said.

“It will also allow the generation of very powerful experimental models in small mammals for the study of drugs that affect the nervous system,” he said.

The procedure might allow scientists to control small organisms and direct them to provide useful services, De Camilli said. Once the technique is perfected, insect pollination could be controlled by flipping a light switch, he said.

“The bottom line is the generation of animal species whose behavior can be controlled,” De Camilli said. “It is a landmark in that respect.”

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