New insights into the mechanisms behind defensive behaviors, like flight-or-freezing responses, were published today in Nature Communications by Salk Institute researchers. Although innate defensive responses are essential to animal survival, the underlying signaling mechanisms behind the response have been poorly understood.
The Salk team studied the response of Caenorhabditis elegans to chemicals secreted by Pristionchus pacificus, its natural predator. When C. elegans encountered predator-excreted chemicals, it rapidly reversed direction and crawled away.
Using mass spec, the team identified the fear-inducing chemical, a new class of molecules called sulfolipids, which could activate four redundant brain circuits that led to this behavior.
"For years, we thought that only advanced brains like those of mammals would have this complex reaction," explained Sreekanth Chalasani, associate professor in Salk's Molecular Neurobiology Laboratory and senior author of the paper. "But our study is showing that a simple animal expresses something very much like fear."
In the experiment, coauthor Amy Pribadi soaked C. elegans in a solution containing the sulfolipid for 30 minutes. The worms failed to lay eggs, even for an hour after they had been removed from the solution—an indicator of acute stress as well as a longer-term response akin to anxiety. Further research showed that the signaling pathways activated during the worms' response are similar to the pathways activated when more complex animals experience fear.
When the worms were soaked in a solution containing Zoloft, however, these fear- and anxiety-like responses were not observed. This suggested that at least some of the pathways that the drug acts on to eliminate anxiety in mammals have been preserved by evolution.
"We hope the findings from this paper will contribute to the field by providing a broader picture of some of these signaling activities," Chalasani says. "Our findings suggest that fear and anxiety are ancient and evolved much earlier than we originally thought. The pathways, nerves, circuits and genes that we'll now be able to study in the worm should inform us about this process in humans."
Image: A C. elegans worm (lower right) exposed to sulfolipid chemicals from one of its natural predators, a worm called P. Pacificus, quickly reverses direction in a response analogous to human fear. Image courtesy of Amy Pribadi