Drosophila vesicular monoamine transporter mutants can adapt to reduced or eliminated vesicular stores of dopamine and serotonin.
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.
Simon
Anne F
AF
Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Daniels
Richard
R
Romero-Calderón
Rafael
R
Grygoruk
Anna
A
Chang
Hui-Yun
HY
Najibi
Rod
R
Shamouelian
David
D
Salazar
Evelyn
E
Solomon
Mordecai
M
Ackerson
Larry C
LC
Maidment
Nigel T
NT
Diantonio
Aaron
A
Krantz
David E
DE
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*
D029721:Drosophila Proteins; D050493:Vesicular Monoamine Transport Proteins; D009655:Octopamine; D012701:Serotonin; D003042:Cocaine; D004298:Dopamine