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Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans

Abstract

Food can be hazardous, either through toxicity or through bacterial infections that follow the ingestion of a tainted food source. Because learning about food quality enhances survival, one of the most robust forms of olfactory learning is conditioned avoidance of tastes associated with visceral malaise. The nematode Caenorhabditis elegans feeds on bacteria but is susceptible to infection by pathogenic bacteria in its natural environment. Here we show that C. elegans modifies its olfactory preferences after exposure to pathogenic bacteria, avoiding odours from the pathogen and increasing its attraction to odours from familiar nonpathogenic bacteria. Particular bacteria elicit specific changes in olfactory preferences that are suggestive of associative learning. Exposure to pathogenic bacteria increases serotonin in ADF chemosensory neurons by transcriptional and post-transcriptional mechanisms. Serotonin functions through MOD-1, a serotonin-gated chloride channel expressed in sensory interneurons, to promote aversive learning. An increase in serotonin may represent the negative reinforcing stimulus in pathogenic infection.

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Figure 1: C. elegans learns to avoid pathogenic bacteria.
Figure 2: Olfactory maze assay.
Figure 3: ADF serotonergic neurons regulate aversive learning.
Figure 4: MOD-1 regulates aversive learning.
Figure 5: Pathogenic bacteria increase serotonin in ADF neurons.

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Acknowledgements

We thank J. N. Engel for P. aeruginosa strains PA14, PAK and PA103; J. Y. Sze for the tph-1::GFP strain; L. Tecott and O. Murphy for assistance with HPLC; L. G. Rahme and F. M. Ausubel for P. aeruginosa strains 50E12, 12A1 and PA14 (gacA::Kan); and J. J. Ewbank for S. marcescens strains Db11 and Db1140 and for comments on the manuscript. Y.Z. was supported by an American Heart Association Postdoctoral Fellowship and the Howard Hughes Medical Institute. H.L. was supported by a Mentored Quantitative Scientist Career Development Award from the NIH and the Howard Hughes Medical Institute. C.I.B. is an investigator of the Howard Hughes Medical Institute. This work was supported by funding from the Howard Hughes Medical Institute (to C.I.B.).Author Contributions Y.Z. and H.L. performed all experiments. C.I.B., Y.Z. and H.L. contributed to experimental design and analysis.

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Correspondence to Cornelia I. Bargmann.

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Supplementary information

Supplementary Methods

Additional descriptions of the methods used in this study. (DOC 53 kb)

Supplementary Figure Legends

Text to accompany the below Supplementary Figures (DOC 43 kb)

Supplementary Figures

This file contains Supplementary Figures 1–8. (PDF 530 kb)

Supplementary Figure 9

Expression of tph-1 in ADF neurons rescues aversive olfactory learning on PA14. Four-choice maze assays of mutants and transgenic strains. (PDF 198 kb)

Supplementary Figure 10

The serotonin-gated chloride channel MOD-1 regulates aversive learning in interneurons. Four-choice maze assays of mutants and transgenic strains. (PDF 211 kb)

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Zhang, Y., Lu, H. & Bargmann, C. Pathogenic bacteria induce aversive olfactory learning in Caenorhabditis elegans. Nature 438, 179–184 (2005). https://doi.org/10.1038/nature04216

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