title: Aging-dependent and -independent modulation of associative learning behavior by insulin/insulin-like growth factor-1 signal in Caenorhabditis elegans.
abstract: Mutations in the insulin/IGF-1 neuroendocrine pathway extend lifespan and affect development, metabolism, and other biological processes in Caenorhabditis elegans and in other species. In addition, they may play a role in learning and memory. Investigation of the insulin/IGF-1 pathway may provide clues for the prevention of age-related declines in cognitive functions. Here, we examined the effects of the life-extending (Age) mutations, such as the age-1 (phosphatidylinositol 3-OH kinase) and daf-2 (insulin/IGF-1 receptor) mutations, on associative learning behavior called isothermal tracking. This thermotaxis learning behavior associates paired stimuli, temperature, and food. The age-1 mutation delayed the age-related decline of isothermal tracking, resulting in a 210% extension of the period that ensures it. The effect is dramatic compared with the extension of other physiological health spans. In addition, young adults of various Age mutants (age-1, daf-2, clk-1, and eat-2) showed increased consistency of temperature-food association, which may be caused by a common feature of the mutants, such as the secondary effects of life extension (i.e., enhanced maintenance of neural mechanisms). The age-1 and daf-2 mutants but not the other Age mutants showed an increase in temperature-starvation association through a different mechanism. Increased temperature-food association of the daf-2 mutant was dependent on neuronal Ca2+-sensor ncs-1, which modulates isothermal tracking in the AIY interneuron. Interestingly, mutations in the daf-7 TGFbeta gene, which functions in parallel to the insulin/IGF-1 pathway, caused deficits in acquisition of temperature-food and temperature-starvation association. This study highlights roles of the Age mutations in modulation of certain behavioral plasticity.
authors.affiliation: Gheens Center on Aging, Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky 40202, USA.
authors.forename: Hana
authors.initials: H
authors.lastname: Murakami
authors.forename: Karalee
authors.initials: K
authors.lastname: Bessinger
authors.forename: Jason
authors.initials: J
authors.lastname: Hellmann
authors.forename: Shin
authors.initials: S
authors.lastname: Murakami
mesh_terms: D000375:Aging / Q000502:physiology* / Q000523:psychology; D000821:Animal Feed; D000818:Animals; D001245:Association Learning / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology; D007328:Insulin / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007395:Interneurons / Q000378:metabolism; D008124:Locomotion / Q000502:physiology; D008136:Longevity / Q000502:physiology; D009043:Motor Activity / Q000502:physiology; D009154:Mutation / Q000502:physiology*; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011972:Receptor, Insulin / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D013217:Starvation; D013696:Temperature; D016212:Transforming Growth Factor beta / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D002135:Calcium-Binding Proteins; D007328:Insulin; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D016212:Transforming Growth Factor beta; C101464:frequenin calcium sensor proteins; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; C100662:AGE-1 protein, C elegans; C107483:DAF-2 protein, C elegans; D011972:Receptor, Insulin; D002118:Calcium