Originally published as Genetics Published Articles Ahead of Print on November 24, 2008.

Genetics, Vol. 181, 525-541, February 2009, Copyright © 2009
doi:10.1534/genetics.108.094110

Drosophila Vesicular Monoamine Transporter Mutants Can Adapt to Reduced or Eliminated Vesicular Stores of Dopamine and Serotonin

Anne F. Simon*,1, Richard Daniels{dagger}, Rafael Romero-Calderón*, Anna Grygoruk*, Hui-Yun Chang*,2, Rod Najibi*, David Shamouelian*, Evelyn Salazar*, Mordecai Solomon*, Larry C. Ackerson*, Nigel T. Maidment*, Aaron DiAntonio{dagger} and David E. Krantz*,3

* Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, Los Angeles, California 90095 and {dagger} Department of Developmental Biology, Washington University School of Medicine, St. Louis, Missouri 63110

3 Corresponding author: Department of Psychiatry and Biobehavioral Sciences and Semel Institute for Neuroscience and Human Behavior, Hatos Center for Neuropharmacology, Gonda (Goldschmied) Neuroscience and Genetics Research Center, Room 3357C, 695 Charles Young Drive South, David Geffen School of Medicine, Los Angeles, CA 90095-1761.
E-mail: dkrantz{at}ucla.edu

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.


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Genetics 2009 181: NP. [Full Text]