Viruses reveal the brain's fright circuits.

If a mischievous child wearing a ghostly sheet or a witch's hat jumps out from behind a bush this Halloween, the surprise may start your heart pounding. Don't be embarrassed. That reaction is natural, part of the fight-or-flight response programmed into many animals.

When startled, an animal may quickly signal its adrenal gland to start pumping out hormones and its cardiovascular system to go into overdrive. For decades, investigators have known that the sympathetic nervous system, a series of neural connections that includes links from the brain to the heart and the adrenal gland, controls this involuntary response.

Yet brain imaging devices have indicated only roughly the brain regions driving the fight-or-flight reaction. Now, using genetically engineered viruses, researchers from Germany and the United States have tracked down specific brain cells that appear to direct both the adrenal and cardiovascular responses.

Using weakened versions of a herpesvirus that kills pigs, researchers tracked back from the organs to the brain cells controlling them. The viruses "infect sequential chains of neurons. . . . It's an extremely high-resolution way of analyzing brain circuits," explains Arthur D. Loewy of Washington University School of Medicine in St. Louis.

Loewy and his colleagues injected one form of the herpesvirus into the adrenal glands of rats and another into the animals' stellate ganglia, the main nerve bundles connecting heart and brain. After 4 days, investigators examined the rats' brains with antibodies that bind to a distinct protein made by each virus. Brain cells in the medulla and hypothalamus showed evidence of infection by both viruses, they report in the Oct. 27 Science.

"It's real solid work and quite innovative," says J. Patrick Card of the University of Pittsburgh, who also uses viruses to unravel brain circuits.

The viral tracking technique has enabled Loewy to examine what kinds of brain cells command the fight-or-flight response. "These viruses are so weak that they don't destroy the chemicals in neurons," he says.

Loewy and his colleagues hope to identify what other parts of the brain connect to the identified command neurons.