This RCDA proposal deals with the investigation of dynamic presynaptic changes in monamine-containing afferents that may occur during aging in brain areas known to regulate balance and gait (ie. striatum and cerebellum). With RCDA support, I hope to remain in a medical school academic environment and focus on age-related changes in the monoaminergic systems of the CNS. I plan to use the time gained through the funding of this grant to 1) increase my commitment to technical development of new in vivo electrochemical techniques that could be useful in aging research, 2) strengthen my existing research collaborations, and 3) to receive additional training from other laboratories to strengthen and expand my aging research program. With RCDA support, the University of Colorado will relieve me of my current clinical laboratory, administrative, and major teaching duties, such that I can concentrate on my scientific development. The research will utilize a rodent model (Fischer 344 rat) to assess age-related changes in dopaminergic inputs to the striatum and noradrenergic afferents to the cerebellum in intact animals. Following balance and coordination measurements in the young mature and aged animals, high-speed in vivo electrochemical methods (5- 25Hz) will be employed to quantitate the magnitude and temporal characteristics of potassium-evoked and electrically induced release of monoamines. Intracranial microdialysis will be employed as an alternative technique to investigate extracellular changes in monoamines and monoamine metabolites, to aid in the further validation of the electrochemical methods. High performance liquid chromatography coupled with electrochemical detection (HPLC-EC) will be used to measure whole tissue levels of monoamines and their metabolites, for correlation with the monoamine release data. Finally, in situ monoamine-containing brain cell transplants into adult hosts will be used as a model system to delineate possible intrinsic versus extrinsic determinants that may be associated with any age-related changes.
