Salk study identifies gene that helps body tell when to de-escalate aggression

The brain mechanisms that cause aggressive behavior have been well-studied. Much less understood are the processes that tell the body when it’s time to stop fighting. Now, scientists at the Salk Institute for Biological Studies in La Jolla say they have identified a gene and a group of cells in the brain that can play a crucial role in suppressing aggression.

The study, based on findings in fruit flies, was published Sept. 7 in Science Advances. It could have implications for human disorders like Parkinson’s disease, which sometimes can cause behavioral changes such as increased aggression and combativeness.

“We’ve found an important mechanism in the brain that normally prevents us from expressing high levels of aggression,” said senior author Kenta Asahina, an assistant professor in Salk’s Molecular Neurobiology Laboratory. “Although our findings are in fruit flies, the same mechanism may be at play in humans, at least at the molecular level, which could help better explain a host of psychiatric diseases.”

De-escalation, or the ability to decide when it’s time to stop fighting, is a vital behavior for survival because it enables animals to adjust their aggressiveness according to the costs and benefits of an encounter with a rival — at a certain point, continuing to fight is no longer worth it. Sensing when it’s time to de-escalate is complex because there isn’t an obvious trigger, such as the way fullness triggers an animal to stop eating.

For the study, scientists compared the behavior of normal fruit flies with fruit flies lacking various genes of interest. Specifically, they examined how frequently male flies lunged at other males, a typical aggressive behavior in that species. They found that flies missing a gene called nervy were significantly more aggressive than their normal counterparts.

The nervy gene isn’t actually involved in the moment-to-moment decision to stop fighting. Rather, it helps give the fly the ability to respond to environmental cues (likely its experience with other individuals), the researchers say.

“The function of nervy is to set up the nervous system in such a way that animals are ready to stop fighting when the right signal comes in,” said first author Kenichi Ishii, a former postdoctoral fellow in Asahina’s lab.

The flies that lacked nervy weren’t initiating more aggressive interactions by chasing other flies. They simply were more likely to choose to fight over the course of a normal encounter.

Researchers then used single-cell sequencing to look at how other genes were activated differently in flies that were missing the nervy gene, compared with normal flies. This enabled the team to identify other genes downstream from nervy that were involved in developing the de-escalation mechanism.

The authors also identified a small group of cells in the brain (neurons) that de-escalate fighting by using the nervy gene.

But more work is necessary to understand the brain circuit that stops fighting. For the next step, the researchers hope to precisely identify the group of neurons responsible for suppressing aggressive behavior. They also want to figure out at what stage of development the nervy gene is important for shaping the nervous system. ◆