The long-term goal of this proposal is to understand how the neurotransmitter dopamine regulates the activities of neurons. Dopamine signaling is involved in learning and memory and abnormal dopamine signaling has been implicated in a variety of mental disorders including schizophrenia, drug addiction, depression, and Parkinson's disease. Despite the importance of understanding how dopamine affects brain function, we do not have a clear understanding of the signaling mechanisms by which dopamine acts. I have developed a genetic strategy to identify the physiological components of dopamine signaling pathways that uses C. elegans as a model. The mechanisms of dopamine signaling are conserved between C. elegans and humans.
My specific aims are: 1) to perform a genetic screen to isolate mutants defective in dopamine signaling and to perform a phenotypic analysis of the mutants using well-established behavioral assays; 2) to clone the signaling genes identified by the mutants and to molecularly analyze their function in dopamine signaling. Genetic analysis has the potential to identify signaling components that, by the nature of the analysis, must be of physiological relevance. This genetic strategy is different than other strategies used previously to identify the components of dopamine signaling. Novel signaling molecules identified by this analysis would represent novel targets for the development of new therapeutic strategies to treat mental disorders associated with defects in dopamine signaling. ? ?
| Wani, Khursheed A; Catanese, Mary; Normantowicz, Robyn et al. (2012) D1 dopamine receptor signaling is modulated by the R7 RGS protein EAT-16 and the R7 binding protein RSBP-1 in Caenoerhabditis elegans motor neurons. PLoS One 7:e37831 |
| Allen, Andrew T; Maher, Kathryn N; Wani, Khursheed A et al. (2011) Coexpressed D1- and D2-like dopamine receptors antagonistically modulate acetylcholine release in Caenorhabditis elegans. Genetics 188:579-90 |
| Chase, Daniel L; Koelle, Michael R (2007) Biogenic amine neurotransmitters in C. elegans. WormBook :1-15 |
