title: Drosophila vesicular monoamine transporter mutants can adapt to reduced or eliminated vesicular stores of dopamine and serotonin.
abstract: Physiologic and pathogenic changes in amine release induce dramatic behavioral changes, but the underlying cellular mechanisms remain unclear. To investigate these adaptive processes, we have characterized mutations in the Drosophila vesicular monoamine transporter (dVMAT), which is required for the vesicular storage of dopamine, serotonin, and octopamine. dVMAT mutant larvae show reduced locomotion and decreased electrical activity in motoneurons innervating the neuromuscular junction (NMJ) implicating central amines in the regulation of these activities. A parallel increase in evoked glutamate release by the motoneuron is consistent with a homeostatic adaptation at the NMJ. Despite the importance of aminergic signaling for regulating locomotion and other behaviors, adult dVMAT homozygous null mutants survive under conditions of low population density, thus allowing a phenotypic characterization of adult behavior. Homozygous mutant females are sterile and show defects in both egg retention and development; males also show reduced fertility. Homozygotes show an increased attraction to light but are mildly impaired in geotaxis and escape behaviors. In contrast, heterozygous mutants show an exaggerated escape response. Both hetero- and homozygous mutants demonstrate an altered behavioral response to cocaine. dVMAT mutants define potentially adaptive responses to reduced or eliminated aminergic signaling and will be useful to identify the underlying molecular mechanisms.
authors.affiliation: Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Simon
authors.forename: Richard
authors.initials: R
authors.lastname: Daniels
authors.forename: Rafael
authors.initials: R
authors.lastname: Romero-Calderón
authors.forename: Anna
authors.initials: A
authors.lastname: Grygoruk
authors.forename: Hui-Yun
authors.initials: HY
authors.lastname: Chang
authors.forename: Rod
authors.initials: R
authors.lastname: Najibi
authors.forename: David
authors.initials: D
authors.lastname: Shamouelian
authors.forename: Evelyn
authors.initials: E
authors.lastname: Salazar
authors.forename: Mordecai
authors.initials: M
authors.lastname: Solomon
authors.forename: Larry C
authors.initials: LC
authors.lastname: Ackerson
authors.forename: Nigel T
authors.initials: NT
authors.lastname: Maidment
authors.forename: Aaron
authors.initials: A
authors.lastname: Diantonio
authors.forename: David E
authors.initials: DE
authors.lastname: Krantz
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D017344:Genes, Insect; D007246:Infertility / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D009469:Neuromuscular Junction / Q000378:metabolism; D009655:Octopamine / Q000378:metabolism; D009866:Oogenesis / Q000235:genetics; D010641:Phenotype; D018462:Photobiology; D012701:Serotonin / Q000378:metabolism; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D050493:Vesicular Monoamine Transport Proteins; D009655:Octopamine; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine