title: GSK-3/Shaggy regulates olfactory habituation in Drosophila.
abstract: Habituation is a universal form of nonassociative learning that results in the devaluation of sensory inputs that have little information content. Although habituation is found throughout nature and has been studied in many organisms, the underlying molecular mechanisms remain poorly understood. We performed a forward genetic screen in Drosophila to search for mutations that modified habituation of an olfactory-mediated locomotor startle response, and we isolated a mutation in the glycogen synthase kinase-3 (GSK-3) homolog Shaggy. Decreases in Shaggy levels blunted habituation, whereas increases promoted habituation. Additionally, habituation acutely regulated Shaggy by an inhibitory phosphorylation mechanism, suggesting that a signal transduction pathway that regulates Shaggy is engaged during habituation. Although shaggy mutations also affected circadian rhythm period, this requirement was genetically separable from its role in habituation. Thus, shaggy functions in different neuronal circuits to regulate behavioral plasticity to an olfactory startle and circadian rhythmicity.
authors.affiliation: Department of Anatomy and Program in Neuroscience, University of California, San Francisco, CA 94143, USA. frederick.wolf@ucsf.edu
authors.forename: Fred W
authors.initials: FW
authors.lastname: Wolf
authors.forename: Mark
authors.initials: M
authors.lastname: Eddison
authors.forename: Seonok
authors.initials: S
authors.lastname: Lee
authors.forename: William
authors.initials: W
authors.lastname: Cho
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
mesh_terms: D000483:Alleles; D000818:Animals; D001522:Behavior, Animal; D002940:Circadian Rhythm; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism / Q000502:physiology*; D000071679:Glycogen Synthase Kinase 3 beta; D006185:Habituation, Psychophysiologic; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D010766:Phosphorylation; D015398:Signal Transduction; D012903:Smell
chemical_list: D029721:Drosophila Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C080335:Sgg protein, Drosophila; D038362:Glycogen Synthase Kinase 3