The general hypothesis is that an important function of the basal ganglia is the processing of sensory as well as motor information to select and facilitate movements in normal states. Because striatal function must depend upon afferent information, the proposed studies define some aspects of this afferent information. Abnormal processing of sensory information in striatum may contribute to the abnormalities seen in Parkinson's disease and several other movement disorders, e.g. Huntington's and dystonias. More specifically, particular aspects of sensory, and parameters of motor function may be affected in the basal ganglia by the loss of dopamine in Parkinson's disease. These studies use C14 deoxyglucose autoradiographic mapping techniques to identify a tactile stimulus as a significant functional event in basal ganglia, to map and quantify the stimulus response throughout the basal ganglia, thalamus and cortex, and to compare this response to muscle afferent stimulation, passive movement and a trained movement of a limb. The somatosensory stimulus intensity will be varied to characterize the normal basal ganglia input-output functions of large groups of neurons, movement amplitude will be varied to confirm that it is a significant parameter processed by basal ganglia. These functions will then be analyzed for their dependence on dopamine for normal processing (metabolic response) in the motor system. The rat model of Parkinson's disease will be used. Lesions of the substantia nigra will be made to selectively damage the dopamine cells with 6 OH dopamine. C14 deoxyglucose studies of the tactile stimulus, of the muscle afferent stimulus, and trained movement will be carried out in the lesion condition. In each of these conditions, not only will basal ganglia metabolism be analyzed in detail, but also metabolism in cortex, thalamus and multiple other brain regions and spinal cord will be analyzed. The contribution of somatosensory cortex to basal ganglia responses under the somatosensory stimulus conditions will also be studied by making an ibotenic acid lesion of the cortex. An overall goal of these studies is to provide data and an approach that can be applied to a variety of animal models of movement disorders, e.g. genetic dystonia (rat model) and the promate MPTP model of Parkinson's disease. This approach may ultimately be applicable to PET studies of human movement disorders.
