51st Annual Drosophila Research ConferenceAbstract #146 PLATFORMS: Neural Physiology and Behavior
Our understanding of the genetic aetiology of alcoholism continues to be overshadowed by what is a debilitating individual and familial problem.
A low level of response to alcohol is a characteristic trait associated with heavy drinking and alcohol problems. Therefore, to discover novel genes that regulate the level of response to ethanol we conducted an unbiased genetic screen for ethanol sensitivity mutants in Drosophila.
We identify the arouser (aru) gene and demonstrate its opposing function in neurons and a subpopulation of glia in the regulation of ethanol sensitivity. Whereas aru functions in neurons to promote ethanol resistance, in glia it functions to inhibit ethanol resistance.
We show that aru acts upstream of, and in opposition to, the function of Akt in regulating ethanol sensitivity in both neurons and glia. Simultaneous manipulations of aru or Akt in neurons and glia show neurons suppress glial mediated effects on ethanol sensitivity. Within neurons aru also mediates Erk/rolled induced increases in ethanol resistance, suggesting Akt and Erk act antagonistically in regulating ethanol sensitivity.
Taken together, this data reveals that ethanol sensitivity in the fly is regulated by both neurons and glia, and by the integration of two major growth factor signaling pathways.
Mark Eddison1, Douglas Guarnieri2, Che Hsiung Liu3, Kevin Moffat3, Ulrike Heberlein1. 1) UCSF, Dept of Anatomy, Box2822, San Francisco, CA 94158; 2) Dept. of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT 06510; 3) Dept of Biological Sciences, University of Warwick, Coventry CV4 7AL, U. K.
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