CANDIDATEMy immediate goals are to continue my research and training in electrophysiology, biological imaging andneuroscience. During the K99 phase (2 years), I will conduct experiments and be trained in electrochemicalrecording methods and multi-photon imaging. I will publish papers and search for a job as an independentfaculty/investigator during the K99 phase, and will transition to the R00 independent phase (3 years) uponsecuring a faculty position. The total duration of the project is 5 years.ENVIRONMENTThe K99 phase of this project will be conducted at the California Institute of Technology, which affords anexcellent research and learning environment for postdoctoral scientists. Caltech has a strong neurosciencecommunity, excellent faculty, and many highly productive and resourceful postdoctoral scholars and graduatestudents for one to collaborate with. Caltech also runs the Biological Imaging Center through the BeckmanInstitute, a resource that will be a very important part of my training plan. For the institution where I willconduct my R00 phase studies, I will choose an institute or university with excellent neuroscience resourcesand faculty that will put me in the best position for growth and success.RESEARCHThis research program is designed to test the hypothesis that specific nicotinic ACh receptors are important formodulating release of neurotransmitters such as dopamine. In particular, I will test the idea that nicotinicreceptors containing 6 subunits, which are found on dopamine presynaptic terminals, are important mediatorsof dopamine release. I will also test the idea that the ability of these receptors to mediate dopamine release isgoverned by their subcellular regulation by the neurons where they reside. Finally, I will test the idea that 6receptor expression and function are significantly altered when animals are exposed to chronic nicotine. Thus,these experiments will determine whether these receptors are important in dopamine release and in disorderssuch as nicotine dependence.To carry out these experiments, I designed and built a set of novel transgenic mouse lines to particularlyisolate aspects of 6 nAChR biology. For example, some experiments will utilize mice with hypersensitive 6receptors that amplify and isolate 6 physiology and behavior, while other experiments will make use of miceexpressing fluorescently-labeled 6 receptors that allow for direct visualization of these proteins in liveneurons.
RELEVANCE TO PUBLIC HEALTH This project is designed to give the research and health care community a better understanding of particular neurotransmitter receptors that may be important in neural disorders such as nicotine dependence, Parkinson's disease, affective disorders, or schizophrenia. The knowledge that will be produced by this research may be useful in designing and testing better drug therapies for these or other related disorders.
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