application) The applicant has identified the cerebellar noradrenergic system as being critical in motor learning processes. Plasticity in the motor system is important for the elderly because many individuals must adapt to new environments and new ways moving around in old environments; in addition, rehabilitation from strokes which affect the motor system required relearning of basic motor skills. Aged animals and humans demonstrate a decline in plasticity of motor learning. Thus understanding this decline in plasticity in aged animals will be of significant importance. They have been examining motor learning in aged rats and have demonstrated that the decline in learning is associated with a loss of cerebellar noradrenergic function. They seek to understand the biological mechanism underlying the age-associated decline in cerebellar noradrenergic receptor function and associated motor behavior. They will examine the signal transduction mechanisms of the B-adrenergic receptor using electrophysiological techniques. They can stimulate the transduction cascade at various points to determine if the deficit in B-adrenergic responsiveness is up or downstream from the point of stimulation. The free radical theory of aging postulates that oxidative stress is a major etiological factor for the decline in physiological functions that eventually lead to death of the organism. Oxidative stress has been implicated to play a major role ir Alzheimer's disease and Parkinson's disease. A second goal of this project is to examine the role of oxidative stress and reactive oxygen species (ROS) in a specific neurobiological model system of aging: the cerebellar noradrenergic system and its role in motor learning. The response of the cerebellar noradrenergic system, in terms of electrophysiology, and motor learning behavior, to oxidative stress will be studied in aged rats and in young rats exposed to normobaric hyperoxia. An important aspect of this research will be in examining the effect of N-tert-butyl-a-phenylnitrone (PBN) and antioxidant drugs on age-related cerebellar noradrenergic function and motor learning. Their initial findings have demonstrated that PBN will improve B-adrenergic receptor function in aged rats. Thus, they will extend this finding to other drugs and to behavioral studies. Career enhancement will concentrate in three main areas, 1 ) learning whole cell record techniques so that the applicant can ask more specific mechanistic questions and 2) learning in situ hybridization techniques and 3 molecular biological techniques for creating knock out animals so that she can address questions at the molecular level.
