The long-term goal of this proposed project is to understand fundamental neuronal mechanisms underlying higher brain functions that control complex behaviors. Disruption of higher brain functions, such as learning and memory, can occur for a number of reasons including brain surgery, chronic alcohol abuse, head injury, anoxia, and various neurodegenerative disorders such as Alzheimer's disease. A basic understanding of how anatomically distinct neurons in the brain communicate with one another to manipulate complex behavior is essential for the prevention and treatment of many disorders affecting higher brain functions. Recent studies indicate that molecules and cellular mechanisms responsible for important biological processes, including learning and memory, are well conserved among distantly related species. In this project, Drosophila male courtship, which consists of a highly stereotypical sequence of activities and also shows considerable experience-dependent plasticity, will be used as a physiological model of higher-order brain functions.
Specific aims of the project are to identify the neuronal subsets involved in the learning/memory process of the courtship plasticity and to determine the temporal requirements of neuronal activity during different phases of the memory formation. To accomplish these aims, a novel molecular genetic approach has been established. In this approach a temperature-sensitive allele of the Drosophila shibire gene (shi"""""""") is expressed in restricted neuronal subsets using the GAL4IUAS system. Then, synaptic transmission of the targeted neurons is blocked rapidly and reversibly by a mild temperature-shift in intact animals. By taking advantage of the large collection of available GAL4 lines that are specific to restricted brain regions, the significance of particular neuronal subsets in the courtship plasticity will be determined. A combination of genetic and morphological analysis will be applied to further investigate the neuronal subsets whose functional significance is revealed. The neuronal subsets involved in the genetically determined, stereotypical aspects of male courtship will be also identified using the same approach. The anticipated results, together with the accumulated information of Drosophila behavioral genetics, will provide new insight into the neuronal mechanisms of higher-brain functions in flies, and will contribute to the development of conceptual frameworks for the study of complex behaviors in higher vertebrates including humans.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH062684-01A2
Application #
6542847
Study Section
Integrative, Functional and Cognitive Neuroscience 8 (IFCN)
Program Officer
Edwards, Emmeline
Project Start
2002-08-01
Project End
2003-07-31
Budget Start
2002-08-01
Budget End
2003-07-31
Support Year
1
Fiscal Year
2002
Total Cost
$350,000
Indirect Cost
Name
City of Hope/Beckman Research Institute
Department
Type
DUNS #
City
Duarte
State
CA
Country
United States
Zip Code
91010
Sakai, Takaomi; Watanabe, Kazuki; Ohashi, Hirono et al. (2014) Insulin-producing cells regulate the sexual receptivity through the painless TRP channel in Drosophila virgin females. PLoS One 9:e88175
Ishimoto, Hiroshi; Wang, Zhe; Rao, Yi et al. (2013) A novel role for ecdysone in Drosophila conditioned behavior: linking GPCR-mediated non-canonical steroid action to cAMP signaling in the adult brain. PLoS Genet 9:e1003843
Sakai, Takaomi; Sato, Shoma; Ishimoto, Hiroshi et al. (2012) Significance of the centrally expressed TRP channel painless in Drosophila courtship memory. Learn Mem 20:34-40
Sakai, Takaomi; Inami, Show; Sato, Shoma et al. (2012) Fan-shaped body neurons are involved in period-dependent regulation of long-term courtship memory in Drosophila. Learn Mem 19:571-4
Ishimoto, Hiroshi; Kitamoto, Toshihiro (2011) Beyond molting--roles of the steroid molting hormone ecdysone in regulation of memory and sleep in adult Drosophila. Fly (Austin) 5:215-20
Aldrich, Benjamin T; Kasuya, Junko; Faron, Matthew et al. (2010) The amnesiac gene is involved in the regulation of thermal nociception in Drosophila melanogaster. J Neurogenet 24:33-41
Ishimoto, Hiroshi; Kitamoto, Toshihiro (2010) The steroid molting hormone Ecdysone regulates sleep in adult Drosophila melanogaster. Genetics 185:269-81
Aso, Yoshinori; Siwanowicz, Igor; Bräcker, Lasse et al. (2010) Specific dopaminergic neurons for the formation of labile aversive memory. Curr Biol 20:1445-51
Kasuya, Junko; Ishimoto, Hiroshi; Kitamoto, Toshihiro (2009) Neuronal mechanisms of learning and memory revealed by spatial and temporal suppression of neurotransmission using shibire, a temperature-sensitive dynamin mutant gene in Drosophila melanogaster. Front Mol Neurosci 2:11
Sakai, T; Kasuya, J; Kitamoto, T et al. (2009) The Drosophila TRPA channel, Painless, regulates sexual receptivity in virgin females. Genes Brain Behav 8:546-57

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