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The Journal of Neuroscience, April 25, 2007, 27(17):4541-4551; doi:10.1523/JNEUROSCI.0305-07.2007

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Cellular/Molecular
Drosophila Homer Is Required in a Small Set of Neurons Including the Ellipsoid Body for Normal Ethanol Sensitivity and Tolerance

Nancy L. Urizar,1 Zhiyong Yang,1 Howard J. Edenberg,3 and Ronald L. Davis1,2

Departments of 1Molecular and Cellular Biology and 2Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, Texas 77030, and 3Department of Biochemistry and Molecular Biology and Center for Medical Genomics, Indiana University School of Medicine, Indianapolis, Indiana 46202

Correspondence should be addressed to Dr. Ronald L. Davis at the above address. Email: rdavis{at}bcm.tmc.edu

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.

Key words: homer; Drosophila; ethanol; sensitivity; tolerance; ellipsoid body

Received Jan. 23, 2007; revised March 13, 2007; accepted March 14, 2007.

Correspondence should be addressed to Dr. Ronald L. Davis at the above address. Email: rdavis{at}bcm.tmc.edu


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