Drosophila homer is required in a small set of neurons including the ellipsoid body for normal ethanol sensitivity and tolerance.
The molecular mechanisms occurring in the nervous system that underlie behavioral responses to ethanol remain poorly understood. Here, we report that molecular requirements for two of these responses, initial sensitivity and the development of rapid tolerance, comap to the same small set of neurons. We show that null homer mutant flies exhibit both increased sensitivity to the sedative effects of ethanol and failure to develop normal levels of rapid tolerance. Both the sensitivity and rapid tolerance phenotypes of the homer mutants are rescued by the expression of wild-type homer in a subset of neurons that include the ellipsoid body. Thus, some of the molecular- and systems-level requirements for these two behavioral responses to ethanol are identical.
Urizar
Nancy L
NL
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Yang
Zhiyong
Z
Edenberg
Howard J
HJ
Davis
Ronald L
RL
D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002492:Central Nervous System Depressants / Q000493:pharmacokinetics / Q000494:pharmacology*; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster; D004351:Drug Resistance / Q000235:genetics; D004361:Drug Tolerance / Q000235:genetics*; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D000072233:Homer Scaffolding Proteins; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D002352:Carrier Proteins; D002492:Central Nervous System Depressants; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C052130:GAL4 protein, S cerevisiae; D000072233:Homer Scaffolding Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C000606630:homer protein, Drosophila; D000431:Ethanol