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The Journal of Neuroscience, September 15, 2000, 20(18):6868-6878
Integrin-Mediated Regulation of Synaptic Morphology, Transmission, and Plasticity
Jeffrey Rohrbough1, Michael S. Grotewiel2, Ronald L. Davis3, and Kendal Broadie1 1 Department of Biology, University of Utah, Salt Lake City, Utah 84112, 2 Department of Zoology, Michigan State University, East Lansing, Michigan 48824-1312, and 3 Department of Cell Biology and Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030
Volado, the gene encoding the Drosophila
PS3-integrin, is required for normal short-term memory formation (Grotewiel et al., 1998), supporting a role for integrins in synaptic modulation mechanisms. We show that the Volado protein (VOL) is localized to central and peripheral larval Drosophila synapses. VOL is strongly concentrated in a subpopulation of synaptic boutons in the CNS neuropil and to a variable subset of synaptic boutons at neuromuscular junctions (NMJs). Mutant morphological and functional synaptic phenotypes were analyzed at the NMJ. Volado mutant synaptic arbors are structurally enlarged, suggesting VOL negatively regulates developmental synaptic sprouting and growth. Mutant NMJs exhibit abnormally large evoked synaptic currents and reduced Ca2+ dependence of transmission. Strikingly, multiple forms of Ca2+- and activity-dependent synaptic plasticity are reduced or absent. Conditional Volado expression in mutant larvae largely rescues normal transmission and plasticity. Pharmacologicially disrupting integrin function at normal NMJs phenocopies features of mutant transmission and plasticity within 30-60 min, demonstrating that integrins acutely regulate functional transmission. Our results provide direct evidence that Volado regulates functional synaptic plasticity processes and support recent findings implicating integrins in rapid changes in synaptic efficacy and in memory formation.
Key words: integrins; synaptic plasticity; synaptic signaling; adhesion; learning and memory; neuromuscular junction; Drosophila
Copyright © 2000 Society for Neuroscience 0270-6474/00/20186868-11$05.00/0
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