We propose to investigate dynamic presynaptic changes in monoamine-containing afferents that may occur during aging in brain areas known to regulate balance and gait (i.e., striatum and cerebellum). The experiments 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, in vivo electrochemical methods will be employed to quantitate the magnitude and temporal characteristics of potassium-evoked and electrically-induced release of monoamines. High performance liquid chromatography coupled with electrochemical detection (HPLC-EC) will be used to measure whole tissue levels of nonoamines and their metabolites, and correlate the levels with the monoamine release data. Finally, in situ monoamine-containing brain cell transplants into adult hosts will be used to delineate possible intrinsic versus extrinsic determinants that may be associated with any age-related changes.
