Figure 2.—

Mutant worms with decreased insulin/IGF-1 signaling are defective in associative learning. (A) Regulatory hierarchy among the components of the insulin/IGF-1 genetic cascade in C. elegans. Arrows indicate activations, bars indicate negative regulatory interactions. DAF-2, the worm insulin/IGF-1 receptor; AGE-1, phosphatidylinositol-3-OH kinase (PI3K); DAF-18, PTEN phosphatase—the only known negative regulator of insulin/IGF-1 signaling; PDK-1, AKT-1, AKT-2, and SGK-1, phosphoinositide-dependent serine/threonine kinases; DAF-16, FOXO forkhead transcription factor. (B) Wild-type and insulin/IGF signaling-defective mutant hermaphrodites maintained at 20° were shifted to 25° and assayed for chemotaxis directly (naive) or conditioned on food-free NGM plates with NaCl. None of these strains displayed significant changes in behavior from the corresponding naives when they were conditioned on NaCl-free plates (data not shown). A genetic null mutation in daf-18, nr2037, improves the ability of hermaphrodites to change behavior. Error bars indicate mean ± standard error.