title: Synapsin function in GABA-ergic interneurons is required for short-term olfactory habituation.
abstract: In Drosophila, short-term (STH) and long-term habituation (LTH) of olfactory avoidance behavior are believed to arise from the selective potentiation of GABAergic synapses between multiglomerular local circuit interneurons (LNs) and projection neurons in the antennal lobe. However, the underlying mechanisms remain poorly understood. Here, we show that synapsin (syn) function is necessary for STH and that syn(97)-null mutant defects in STH can be rescued by syn(+) cDNA expression solely in the LN1 subset of GABAergic local interneurons. As synapsin is a synaptic vesicle-clustering phosphoprotein, these observations identify a presynaptic mechanism for STH as well as the inhibitory interneurons in which this mechanism is deployed. Serine residues 6 and/or 533, potential kinase target sites of synapsin, are necessary for synapsin function suggesting that synapsin phosphorylation is essential for STH. Consistently, biochemical analyses using a phospho-synapsin-specific antiserum show that synapsin is a target of Ca(2+) calmodulin-dependent kinase II (CaMKII) phosphorylation in vivo. Additional behavioral and genetic observations demonstrate that CaMKII function is necessary in LNs for STH. Together, these data support a model in which CaMKII-mediated synapsin phosphorylation in LNs induces synaptic vesicle mobilization and thereby presynaptic facilitation of GABA release that underlies olfactory STH. Finally, the striking observation that LTH occurs normally in syn(97) mutants indicates that signaling pathways for STH and LTH diverge upstream of synapsin function in GABAergic interneurons.
authors.affiliation: National Centre for Biological Sciences, Bangalore 560065, India, Institute for Clinical Neurobiology, University of Würzburg, 97078 Würzburg, Germany, Department of Genetics for Learning and Memory, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany, School of Genetics and Microbiology, School of Natural Sciences, Smurfit Institute of Genetics and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin-2, Ireland.
authors.forename: Madhumala K
authors.initials: MK
authors.lastname: Sadanandappa
authors.forename: Beatriz
authors.initials: B
authors.lastname: Blanco Redondo
authors.forename: Birgit
authors.initials: B
authors.lastname: Michels
authors.forename: Veronica
authors.initials: V
authors.lastname: Rodrigues
authors.forename: Bertram
authors.initials: B
authors.lastname: Gerber
authors.forename: K
authors.initials: K
authors.lastname: VijayRaghavan
authors.forename: Erich
authors.initials: E
authors.lastname: Buchner
authors.forename: Mani
authors.initials: M
authors.lastname: Ramaswami
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D004330:Drosophila; D059330:GABAergic Neurons / Q000378:metabolism*; D006185:Habituation, Psychophysiologic / Q000502:physiology*; D007395:Interneurons / Q000378:metabolism*; D055696:Olfactory Perception / Q000502:physiology*; D010766:Phosphorylation; D012903:Smell / Q000502:physiology; D013569:Synapses / Q000378:metabolism; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016704:Synapsins; D005680:gamma-Aminobutyric Acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2