The parasagittal organization of the cerebellar cortex has been demonstrated using numerous methodologies, including morphological, biochemical and physiological approaches. These studies, in numerous species, illustrate the apparent commonality of this organizational schema across species and allude to its importance in the function of the cerebellum in the control, coordination and execution of motor behavior. It is essential to analyze these patterns in the same animal in order to determine whether there is an underlying unitary organizational schema to the cerebellum. Recent studies demonstrate that the climbing fiber afferent system, which originates from the inferior olivary complex, share common boundaries with the distribution of the Purkinje cell specific antigen Zebrin 1. Additional studies in the mouse demonstrate identical parasagittal compartments for the Zebrin 1 antigen and the hydrolytic enzyme 5'-nucleotidase. These studies suggest a common compartmentation for these three different features of cerebellar heterogeneity. In this application, we propose to build on these findings and continue our analysis of parasagittal compartmentation by examining the organization of the other major afferent system, mossy fibers, and the cerebellar cortical efferents. Toward this end the following studies will be conducted in the rodent. (1) Analyze the topographic relationship between mossy fiber afferents to the cerebellar cortex. Such projections from the spinal cord, lateral reticular nucleus, basilar pontine nucleus, vestibular nuclei, external cuneate nucleus and trigeminal nuclei will be analyzed utilizing a double anterograde labeling paradigm. (2) Compare the topographic organization of these mossy fiber projections to the distribution of the Zebrin 1 antigen. This will be accomplished by combined anterograde tracer and immunohistological analysis within the same animal. (3) Analyze the efferent projection of Purkinje cells in the cerebellar cortex, as determined by retrograde tracer analysis, and compare this with the distribution of the Zebrin 1 antigen. These studies will provide essential data which will significantly increase our understanding of cerebellar heterogeneity and thereby help test the hypothesis of a common blueprint for these heterogeneities. The ultimate goal being to develop a more complete understanding of the structural and functional organization of the cerebellum and its influence on normal motor behavior, and abnormal motor behaviors which result from cerebellar disease.
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