AGE RELATED CHANGE IN GLUTAMATE RECEPTORS

点击翻译按钮获取中文摘要

The candidate, Dr. Kathy R. Magnusson, has earned both a ph.D. and a veterinary medical degree and is currently an assistant professor in the Department of Anatomy and Neurobiology at Colorado State University currently an assistant professor in the Department of Anatomy and Neurobiology at Colorado State University. I have an independent, productive research laboratory and teach in the veterinary medical curriculum. I am currently funded by an NIH FIRST award to study the effects of aging on NMDA receptor function. My immediate goals are to move toward incorporating molecular biology approaches into my research program, which will require additional training. My long-term goals are to characterize age-related changes that occur in the brain with particular emphasis on those that effect learning and memory processes and to design interventions that will reduce or alleviate these age-related declines. Recent findings in my research suggest that changes in the subunit composition of the NMDA receptor might account for some of the age-related changes I see in the NMDA receptor. Therefore, it seems crucial that I become proficient in molecular biology techniques in order to explore this important new avenue in my research program. This award would allow me the time to immerse myself in learning these new techniques, to better supervise and analyze the currently funded projects, and to devote more time to scholarly investigation. My department Chair will support this award by reducing my teaching and service to research-related areas, continuing to advise me on career and research issues and allowing me a sabbatical leave in year 5. I have the resources here at Colorado State University to conduct the planned experiments, including the two techniques I plan to learn. I also have faculty here or at the University of Colorado Boulder and the Health Sciences Center to instruct me in these techniques. in addition, CSU has faculty with a concentrated interest in the neuroscience and provides me with exposure to many invited neuroscientist from around the world. The research plan is designed to address the hypothesis that there is a change in affinity of NMDA receptors for glutamate that is alterable experimentally. The proposed investigation includes the following specific aims; 1) Determine if the entire NMDA receptor complex is lost during aging with the use of autoradiographic techniques. 2) Determine if the change in NMDA binding sites is due to loss or change in receptor affinity. 3) Determine what other age-related factors, such as protein concentration or cell loss could account for decreases in binding to NMDA receptors. 4) Determine whether there is an alterable decrease inn electrophysiological responses involving NMDA receptors. 5) Determine there is an alterable change in the performance of a spatial memory task with aging. The new aims of this award are; 6) To learn in situ hybridization techniques and 7) To learn the oocyte/RNA expression system. Both aims are designed to determine whether age-related changes in the receptor subunit composition occur with aging. The time and opportunities provided to me by this award will strengthen my knowledge in the field of aging and my ability to formulate pertinent questions and pursue the answers to the problems that aging induces in the brain.