GSK-3/Shaggy regulates olfactory habituation in Drosophila

doi:10.1073/pnas.0700493104

GSK-3/Shaggy regulates olfactory habituation in Drosophila

*Department of Anatomy and
^¶Program in Neuroscience, University of California, San Francisco, CA 94143; and
^†Ernest Gallo Clinic and Research Center, University of California, Emeryville, CA 94608

Communicated by Yuh Nung Jan, University of California School of Medicine, San Francisco, CA, January 19, 2007 (received for review October 31, 2006)

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.

behavior

Footnotes

^‡To whom correspondence should be addressed at:
Ernest Gallo Clinic and Research Center, 5858 Horton St., Suite 200, Emeryville, CA 94608.
E-mail: frederick.wolf{at}ucsf.edu
Author contributions: F.W.W. and U.H. designed research; F.W.W., M.E., S.L., and W.C. performed research; F.W.W. and M.E. analyzed data; and F.W.W. and U.H. wrote the paper.
↵ ^§Present address: Merck & Co., Inc. UG4D-48, P.O. Box 1000, North Wales, PA 19454-1099.
The authors declare no conflict of interest.
This article contains supporting information online at www.pnas.org/cgi/content/full/0700493104/DC1.
Abbreviation:

GSK-3,

glycogen synthase kinase.