Decoding the Chemistry of Fear


Salk Institute

Illustration of C.elegans wormIn this illustration, 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.Credit: Amy PribadiAsk a dozen people about their greatest fears, and you'll likely get a dozen different responses. That, along with the complexity of the human brain, makes fear—and its close cousin, anxiety—difficult to study. For this reason, clinical anti-anxiety medicines have mixed results, even though they are broadly prescribed. In fact, one in six Americans takes a psychiatric drug.


"For the past 30 or 40 years, scientists have used simpler animals to figure out how fear might work in humans," says Sreekanth Chalasani, associate professor in Salk's Molecular Neurobiology Laboratory and senior author of the paper, published in Nature Communications. "The idea has been that if you could figure out which underlying signals in the brain are related to fear and anxiety, you could develop better drugs to block them."



"For years, we thought that only advanced brains like those of mammals would have this complex reaction," Chalasani says. "But our study is showing that a simple animal expresses something very much like fear."


When the worms were soaked in a solution containing Zoloft (a human anti-anxiety drug), 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.

Also intriguingly, the team found that Zoloft acted on the worms' GABA signaling in a neuron that affects the animal's sleep. Whether this is also the case in humans is not yet known, but points to a potential pathway to understand why Zoloft works in some people and not others. The research eventually could lead to a change in how these drugs are prescribed.

"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."

In addition, he says, understanding which chemicals may repel nematodes could have implications for developing new kinds of pesticides, potentially ones that are even nontoxic. "C. elegans is not a pathogen, but many other types of nematodes can do severe damage to crops," he explains. "Biology research can go in many different directions, and you never know what you're going to uncover."