An animals ability to avoid food with harmful effects is essential for its survival. C. elegans feeds on bacteria in soil, potentially including pathogenic bacteria. For example, two common gram-negative soil bacteria, Pseudomonas aeruginosa (1) and Serratia marcescens (2), can proliferate in C. elegans intestine and cause death. Therefore, learning to avoid toxic food like pathogens could help C. elegans to survive in its natural habitat. Using an olfactory choice assay we found that animals raised on S. marcescens or P. aeruginosa supplemented with a small amount of OP50 avoided the pathogen when it was presented in an olfactory choice assay with OP50, while animals raised on OP50 without being exposed to pathogens did not show strong preferences between the pathogen and OP50. This experience-based change in olfactory preferences appears to represent a form of associative learning similar to taste aversion, a form of learning found in many animals.Adult animals exposed to pathogens acquire an aversion for it in a few hours, indicating that olfactory learning is an acute modification of animals innate preferences. Different pathogens induce olfactory changes specific to animals experiences and learning to avoid pathogens is distinct from adaptation. Using a multiple-choice assay, we found that trained animals acquired both an aversion to the pathogen and an increased attraction for the nonpathogenic bacteria that they were raised on.To identify modulatory pathways in olfactory learning to pathogens, we tested
tph-1 mutants, which are selectively defective in serotonin synthesis.
tph-1 animals are deficient in both attractive and aversive learning in multiple-choice assays, indicating a regulatory role of serotonin in the learning. Increased serotonin contents are detected by HPLC in animals exposed to pathogens; enhanced serotonin immunoreactivity is specifically detected in one pair of serotonergic neurons, ADF. Expression of
tph-1 cDNA in ADF neurons fully rescues aversive learning of
tph-1 mutants. Downstream of ADF, we identified MOD-1, a serotonin-gated chloride channel, as a receptor that functions in interneurons to promote aversive learning. Our results indicate that exposure to pathogenic bacteria enhances serotonergic signaling in ADF neurons, stimulating aversive olfactory learning to pathogens through MOD-1.Reference: (1). M.W. Tan, et al., Proc Natl Acad Sci U S A 96 (1999), 715-20. (2). N. Pujol, et al., Curr Biol 11 (2001), 809-821.