Worms sniff out harm

Serotonin signal warns Caenorhabditis elegans of toxic meal

By | November 10, 2005

Worms can learn to avoid substrates scented with bacteria that have made them sick in the past, and the neurotransmitter serotonin appears to control this aversion, according to a report this week in Nature. Serotonin also mediates nausea and food aversions in humans, suggesting that the chemical serves as an important, well-preserved link between gut and brain, according to the authors.

"This is the first example of associative learning found in C. elegans," said Ikue Mori of Nagoya University in Japan, who studies learning and memory in the animals. Researchers have characterized all 302 neurons in the worm's nervous system, and their connections with each other, but still know little about how they work together to coordinate complex behaviors. "Now, we are trying to know the function of these circuits – what's going on during learning," said Mori, who was not involved in the current study.

C. elegans are soil nematodes that eat bacteria. Some strains of bacteria, however, can infect worms' guts. "They get into the stomach and then go into the intestine where they attach and some of them start growing," senior author Cori Bargmann of Rockefeller University in New York told The Scientist. The infections can be fatal, she said.

Working in Bargmann's lab, biologist Yun Zhang raised C. elegans either on a harmless strain of bacteria or on plates that also held an additional, toxic strain. Naïve worms that had never been infected by harmful bacteria failed to avoid pathogenic bacteria when given a choice between the two strains. But C. elegans that had previous contact with pathogenic bacteria preferred the harmless kind, moving toward a patch that are good to eat and avoiding harmful bacteria.

In further experiments, the group showed that adult C. elegans take only hours to form a preference for harmless bacteria. The authors placed the worms in star-shaped mazes, designed by co-author Hang Lu, which held extracts of noxious bacteria or harmless strains at the end of each arm. Each arm carried one of 4 scents: extracts from the two strains the animals had previously encountered and scents from two additional strains – one harmful and the other not. Within 4 hours, C. elegans spurned the arms carrying extracts from the familiar pathogen, but showed no preference among the other choices.

The team also found that serotonin appears to mediate which scent C. elegans prefers. Repeating the same experiments, the authors showed that mutant C. elegans that are unable to synthesize serotonin, and those lacking a specific receptor for serotonin, failed to learn to avoid the harmful bacteria. The deficit is not likely due to an inability to discriminate the different odors, the scientists report -- when given a choice between novel, non-toxic strains of bacteria, mutant worms preferred the same strains as wild-type worms.

In addition, after bacterial infection, levels of serotonin rapidly increased within chemical-sensing neurons called ADF cells. "We nearly fell out of our chairs when we realized that these neurons were just massively pumping out serotonin," said Bargmann. The cells ramped up their ability to generate serotonin in several stages, she noted, "as though they were saving information about what had gone wrong for longer and longer periods of time." The extended signal may be what generates the lasting behavioral change, she said.

This serotonin-based system for detecting -- and then avoiding -- food that causes illness is found in nearly every animal studied so far, according to Michael Gershon of Columbia University in New York, who studies the gut nervous system in humans. In humans, most serotonin is made in cells lining the intestines, not in the brain, said Gershon, who was not involved in the study. When released, serotonin induces the queasiness we associate with intestinal distress, he said. "Nausea evolved to punish an animal for eating what they shouldn't."

Serotonin is also found in animals as primitive as hydra, which lack a central nervous system, Gershon noted – suggesting that the molecule carries a distress signal so important for protecting against pathogens that it has been preserved through evolutionary time.

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