PT - JOURNAL ARTICLE AU - Felicia K. Ooi AU - Veena Prahlad TI - Olfactory learning primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperone genes in <em>C. elegans</em> AID - 10.1101/152736 DP - 2017 Jan 01 TA - bioRxiv PG - 152736 4099 - http://biorxiv.org/content/early/2017/08/08/152736.short 4100 - http://biorxiv.org/content/early/2017/08/08/152736.full AB - Learning, a process by which animals modify their behavior as a result of experience, allows organisms to synthesize information from their surroundings to acquire resources and predict danger. Here we show that prior encounter with the odor of pathogenic bacteria prepares Caenorhabditis elegans to survive actual exposure to the pathogen by increasing HSF-1-dependent expression of genes encoding molecular chaperones. Learning-mediated enhancement of chaperone gene expression requires serotonin. Serotonin primes HSF-1 to enhance the expression of molecular chaperone genes by promoting its localization to RNA polymerase IIā€“enriched nuclear loci, even prior to transcription. HSF-1-dependent chaperone gene expression ensues, however, only if and when animals encounter the pathogen. Thus, learning equips C. elegans to better survive environmental dangers by pre-emptively and specifically initiating transcriptional mechanisms throughout the whole organism. These studies provide one plausible basis for the protective role of environmental enrichment in disease.