title: arouser reveals a role for synapse number in the regulation of ethanol sensitivity.
abstract: A reduced sensitivity to the sedating effects of alcohol is a characteristic associated with alcohol use disorders (AUDs). A genetic screen for ethanol sedation mutants in Drosophila identified arouser (aru), which functions in developing neurons to reduce ethanol sensitivity. Genetic evidence suggests that aru regulates ethanol sensitivity through its activation by Egfr/Erk signaling and its inhibition by PI3K/Akt signaling. The aru mutant also has an increased number of synaptic terminals in the larva and adult fly. Both the increased ethanol sensitivity and synapse number of the aru mutant are restored upon adult social isolation, suggesting a causal relationship between synapse number and ethanol sensitivity. We thus show that a developmental abnormality affecting synapse number and ethanol sensitivity is not permanent and can be reversed by manipulating the environment of the adult fly.
authors.affiliation: Department of Anatomy, University of California San Francisco, San Francisco, CA 94158, USA. mark.eddison@ucsf.edu
authors.forename: Mark
authors.initials: M
authors.lastname: Eddison
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Guarnieri
authors.forename: Ling
authors.initials: L
authors.lastname: Cheng
authors.forename: Che-Hsiung
authors.initials: CH
authors.lastname: Liu
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Moffat
authors.forename: Graeme
authors.initials: G
authors.lastname: Davis
authors.forename: Ulrike
authors.initials: U
authors.lastname: Heberlein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D007814:Larva; D009154:Mutation / Q000235:genetics*; D009469:Neuromuscular Junction / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D018010:Receptors, Invertebrate Peptide / Q000235:genetics / Q000378:metabolism; D012018:Reflex / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D012934:Social Isolation; D013569:Synapses / Q000187:drug effects / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029681:Arabidopsis Proteins; D002492:Central Nervous System Depressants; D029721:Drosophila Proteins; D018010:Receptors, Invertebrate Peptide; C560424:aru protein, Drosophila; D049452:Green Fluorescent Proteins; D000431:Ethanol; D019869:Phosphatidylinositol 3-Kinases; C066532:Egfr protein, Drosophila; D066246:ErbB Receptors