The long-range goal of the proposed work is to clarify the neuroanatomical organization of circuits in the brain that mediate the basal ganglia (BG) control of movement. The current concept of BG control of motor function emphasizes the importance of the pallido-thalamo-cortical and nigro-thalamo-cortical circuits which link the output nuclei of the BG, i.e. the medial pallidal segment and the pars reticulata of the substantia nigra (SNR), to the premotor cortex. However, several lines of evidence have recently suggested that the BG may also influence the spinal motor system through a more direct route involving the connections from the output nuclei of the BG, particularly those from the SNR, to the nucleus tegmenti pedunculopontinus (PPN). The PPN is located in the pontomesencephalic tegmentum within a physiologically defined mesencephalic locomotor region (MLR) and presumably affects movement through the reticulospinal tracts. To explore the pathways linking the SNR to PPN and PPN to the reticular nuclei projecting to the spinal cord, we propose to employ an anterograde transport technique using the plant lectin Phaseolus vulgaris-leucoag-glutinin (PHA-L). The advantages of this method are that PHA-L is not taken up by fibers-of-passage, is transported only in the anterograde direction, is extremely sensitive, labels axons with the clarity of intracellular HRP labeling, and can be visualized at both the light and electron microscopic levels. In addition, the PHA-L technique is compatible with horseradish peroxidase (HRP) histochemistry which will be used to demonstrate retrogradely labeled spinal cord projecting cells. Specifically, it is proposed to: 1) delineate the SNR and PPN projections to the reticular substance of the brainstem; 2) confirm the terminal fields of these projections ultrastructurally; and 3) examine light and electron microscopically in double-labeling experiments whether the nigral and PPN fibers terminate directly on the spinal cord projecting reticular cells, and whether nigral fibers terminate on the descending PPN neurons. These studies will lay the necessary groundwork for a correct interpretation of physiological and pharmacological data and, in conjunction with such data, will lead to better understanding of the mechanisms involved in the BG control of movement in health and disease.
