Olfactory experience primes the heat shock transcription factor HSF-1 to enhance the expression of molecular chaperones in C. elegans.

Learning, a process by which animals modify their behavior as a result of experience, enables organisms to synthesize information from their surroundings to acquire resources and avoid danger. We showed that a previous encounter with only the odor of pathogenic bacteria prepared Caenorhabditis elegans to survive exposure to the pathogen by increasing the heat shock factor 1 (HSF-1)-dependent expression of genes encoding molecular chaperones. Experience-mediated enhancement of chaperone gene expression required serotonin, which primed HSF-1 to enhance the expression of molecular chaperone genes by promoting its localization to RNA polymerase II-enriched nuclear loci, even before transcription occurred. However, HSF-1-dependent chaperone gene expression was stimulated only if and when animals encountered the pathogen. Thus, learning equips C. elegans to better survive environmental dangers by preemptively and specifically initiating transcriptional mechanisms throughout the whole organism that prepare the animal to respond rapidly to proteotoxic agents. These studies provide one plausible basis for the protective role of environmental enrichment in disease.