AUTHOR=White Katherine E., Humphrey Dickon M., Hirth Frank 

TITLE=The Dopaminergic System in the Aging Brain of Drosophila

JOURNAL=Frontiers in Neuroscience

VOLUME=4

YEAR=2010

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2010.00205

DOI=10.3389/fnins.2010.00205

ISSN=1662-453X

ABSTRACT=<p><italic>Drosophila</italic> models of Parkinson's disease are characterized by two principal phenotypes: the specific loss of dopaminergic (DA) neurons in the aging brain and defects in motor behavior. However, an age-related analysis of these baseline parameters in wildtype <italic>Drosophila</italic> is lacking. Here we analyzed the DA system and motor behavior in aging <italic>Drosophila</italic>. DA neurons in the adult brain can be grouped into bilateral symmetric clusters, each comprising a stereotypical number of cells. Analysis of <italic>TH</italic> &gt; <italic>mCD8::GFP</italic> and cell type-specific MARCM clones revealed that DA neurons show cluster-specific, stereotypical projection patterns with terminal arborization in target regions that represent distinct functional areas of the adult brain. Target areas include the mushroom bodies, involved in memory formation and motivation, and the central complex, involved in the control of motor behavior, indicating that similar to the mammalian brain, DA neurons in the fly brain are involved in the regulation of specific behaviors. Behavioral analysis revealed that <italic>Drosophila</italic> show an age-related decline in startle-induced locomotion and negative geotaxis. Motion tracking however, revealed that walking activity, and exploration behavior, but not centrophobism increase at late stages of life. Analysis of <italic>TH</italic> &gt; <italic>Dcr2</italic>, <italic>mCD8::GFP</italic> revealed a specific effect of <italic>Dcr2</italic> expression on walking activity but not on exploratory or centrophobic behavior, indicating that the siRNA pathway may modulate distinct DA behaviors in <italic>Drosophila</italic>. Moreover, DA neurons were maintained between early- and late life, as quantified by <italic>TH</italic> &gt; <italic>mCD8::GFP</italic> and anti-TH labeling, indicating that adult onset, age-related degeneration of DA neurons does not occur in the aging brain of <italic>Drosophila</italic>. Taken together, our data establish baseline parameters in <italic>Drosophila</italic> for the study of Parkinson's disease as well as other disorders affecting DA neurons and movement control.</p>