Integrin-mediated regulation of synaptic morphology, transmission, and plasticity

Volado, the gene encoding the Drosophila alpha PS3-integrin, is required fo r normal short-term memory formation (Grotewiel et al., 1998), supporting a role for integrins in synaptic modulation mechanisms. We show that the Vol ado protein (VOL) is localized to central and peripheral larval Drosophila synapses. VOL is strongly concentrated in a subpopulation of synaptic bouto ns in the CNS neuropil and to a variable subset of synaptic boutons at neur omuscular junctions (NMJs). Mutant morphological and functional synaptic ph enotypes were analyzed at the NMJ. Volado mutant synaptic arbors are struct urally 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 a bsent. Conditional Volado expression in mutant larvae largely rescues norma l transmission and plasticity. Pharmacologicially disrupting integrin funct ion at normal NMJs phenocopies features of mutant transmission and plastici ty within 30-60 min, demonstrating that integrins acutely regulate function al transmission. Our results provide direct evidence that Volado regulates functional synaptic plasticity processes and support recent findings implic ating integrins in rapid changes in synaptic efficacy and in memory formati on.