title: Effects of sex and insulin/insulin-like growth factor-1 signaling on performance in an associative learning paradigm in Caenorhabditis elegans.
abstract: Learning is an adaptive change in behavior in response to environmental stimuli. In mammals, there is a distinct female bias to learn skills that is still unprecedented in other animal taxa. Here we have investigated the biological determinants of performance in an associative learning paradigm in the nematode Caenorhabditis elegans. Using an assay of chemotactic reactions associated with food deprivation, wild-type male worms show inferior learning ability relative to hermaphrodites. Sex-based learning difference is therefore an ancient evolutionary feature appearing even in relatively simple animals. C. elegans mutants with reduced insulin/IGF-1 signaling also exhibit a greatly reduced learning ability in this assay. In addition, hyperactivation of insulin/IGF-1 signaling through loss-of-function mutations in the PTEN phosphatase daf-18, a negative regulator of insulin/IGF-1 signaling, enhances learning ability beyond that of wild type. According to our epistasis analysis, the effect of DAF-2 on learning acts via phosphatidylinositol 3,4,5-trisphosphate (PIP(3)) production, but not the DAF-16 FOXO transcription factor. This implies that the signaling pathway from DAF-2 affecting this learning paradigm branches between PIP(3) production and DAF-16. However, learning capacity of nematodes is lowered by loss-of-function mutations in daf-16, suggesting involvement of noninsulin/IGF-1 signaling-dependent DAF-16 activation in learning. Potentially, sex and insulin/IGF-1 signaling affect performance in this learning assay via effects on the neurobiology of learning.
authors.affiliation: Department of Genetics, Eötvös Loránd University, Budapest, H-1117, Hungary. vellai@falco.elte.hu
authors.forename: Tibor
authors.initials: T
authors.lastname: Vellai
authors.forename: Diana
authors.initials: D
authors.lastname: McCulloch
authors.forename: David
authors.initials: D
authors.lastname: Gems
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001245:Association Learning / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D003214:Conditioning, Classical / Q000502:physiology; D005260:Female; D051858:Forkhead Transcription Factors; D007328:Insulin / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000502:physiology*; D008297:Male; D008954:Models, Biological; D009154:Mutation; D012727:Sex Characteristics; D012737:Sex Factors; D015398:Signal Transduction; D012965:Sodium Chloride / Q000494:pharmacology; D013217:Starvation; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; C116661:DAF-18 protein, C elegans; D051858:Forkhead Transcription Factors; D007328:Insulin; D014157:Transcription Factors; C108831:daf-16 protein, C elegans; D012965:Sodium Chloride; D007334:Insulin-Like Growth Factor I