Teaching worms good taste: Researcher reveals the cell biology of learning at ASCB meeting

SAN FRANCISCO, CA, DEC. 13, 2005-- Survival is an acquired taste. The worm, C. elegans, lives in soil and feeds on different bacteria, including potentially pathogenic ones. But good taste is not innate in worms. This makes olfactory learning a required subject for C. elegans, a creature with 302 neurons and a nervous system so simple that it is possible to map the individual neurons responsible for specific behaviors. Many of the genes that drive the nervous system of C. elegans have human homologs. Therefore, by studying the education of young worm gourmets, researcher Yun Zhang developed a model system for learning that may extend to humans in places like the Rockefeller University where Zhang is a postdoctoral fellow in the laboratory of Cori Bargmann.

At the ASCB meeting in San Francisco, Zhang will discuss her "worm school" experiments just published in "Nature" (10 November 2005: Vol. 438:179-184) with journalists at the "TEN AM Press Briefing" on Tuesday (Dec. 13) in Room 212 of the Moscone before her talk later in the day to the "Building Sensory Networks" Minisymposium.

"Worms learn from their mistakes," says Zhang. Some pathogenic strains of common soil bacteria Pseudomonas aeruginosa and Serratia marcescens can proliferate in the worm gut. Overindulgence in these pathogens can be fatal. Zhang set up a worm school for olfactory learning, raising one group of worms on a diet of E. coli OP50, a standard lab worm food, and a second group on pathogens, either S. marcescens or P. aeruginosa, supplemented with some OP50. For a final exam, the researcher offered her worms a choice between OP50 and the pathogens. Adult worms raised on the toxic diet took one sniff of the pathogens and headed for OP50. Those raised on OP50 didn't know the difference. They dug in without preference.

"This experience-based olfactory change is distinct from adaptation and appears to represent a form of associative learning, similar to taste aversion," says Zhang. "Adult animals exposed to pathogens acquire an aversion within a few hours, indicating that olfactory learning is an acute modification of the animals' innate preferences."

The key is serotonin, a neurotransmitter known to regulate behaviors in everything from the sea slug Aplysia to humans. Zhang traced olfactory learning in C. elegans to a pair of ADF neurons that produce serotonin. Worms trained through bitter experience to recognize pathogens in their diet had higher serontonin levels in their ADF neurons compared to animals raised on OP50. Zhang then applied the pathogen learning test to groups of tph-1 mutants, worms genetically defective for serotonin synthesis. Without the tph-1 gene to synthesize serotonin, the mutants were unable to learn the good stuff from the bad. By putting the tph-1 gene back to their ADF neurons, Zhang rescued the mutants' ability to learn aversion. Further experiments also identified a serotonin-gated chloride channel, MOD-1, functioning in interneurons downstream of ADF to promote aversive learning. Apparently the worm learns to eat right, one bad taste and one serotonin surge at a time.

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