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The Journal of Neuroscience, November 1, 2002, 22(21):9490-9501
Functional Dissection of Neuroanatomical Loci Regulating Ethanol
Sensitivity in Drosophila
Aylin R.
Rodan1, 3,
John
A.
Kiger Jr4, and
Ulrike
Heberlein1, 2, 3
1 Department of Anatomy and Programs in
2 Neuroscience and 3 Biological Sciences,
University of California, San Francisco, California 94143-0452, and
4 Department of Molecular and Cellular Biology, University
of California, Davis, California 95616
Ethanol has complex but similar effects on behavior in mammals and
the fruit fly Drosophila melanogaster. In addition,
genetic and pharmacological approaches have implicated the cAMP pathway in the regulation of ethanol-induced behaviors in both flies and rodents. Here we examine the neuroanatomical loci that modulate ethanol
sensitivity in Drosophila by targeting the expression of
an inhibitor of cAMP-dependent protein kinase (PKA) to specific regions
in the fly's brain. Expression of the inhibitor in most brain regions
or in muscle has no effect on behavior. In contrast, inhibition of PKA
in a relatively small number of cells, possibly neurosecretory cells,
in the fly's brain is sufficient to decrease sensitivity to the
incoordinating effects of ethanol. Additional brain areas are, however,
also involved. The mushroom bodies, brain structures where cAMP
signaling is required for olfactory classical conditioning, are
dispensable for the regulation of ethanol sensitivity. Finally,
different behavioral effects of ethanol, motor incoordination and
sedation, appear to be regulated by PKA function in distinct brain
regions. We conclude that the regulation of ethanol-induced behaviors
by PKA involves complex interactions among groups of cells that mediate
either increased or reduced sensitivity to the acute intoxicating
effects of ethanol.
Key words:
Drosophila; ethanol; PKA; neuroanatomy; mushroom bodies; postural control; locomotion
Copyright © 2002 Society for Neuroscience 0270-6474/02/22219490-12$05.00/0
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