Topographic and zonal organization of the olivocerebellar projection in the reeler mutant mouse

Abstract

The organization of the olivocerebellar projection in the homozygous reeler mouse (rl/rl) was studied with the use of microinjections of 3H-leucine in different regions of the inferior olivary complex (IO) or horseradish peroxidase conjugated with wheat germ agglutinin (WGA-HRP) into medial, intermediate, or lateral regions of the reeler cerebellum. The purpose of this investigation was to determine the pattern of termination of olivocerebellar climbing fibers (CFs) in the cerebellum via an anterograde tracing technique, and to determine the topographic organization of the olivocerebellar projection via both anterograde and retrograde methods. The inferior olive injections were made via the ventral (i.e., retropharygeal) approach to the IO to minimize diffusion into other brainstem precerebellar nuclei and thus to ensure accurate well-restricted, injection sites. Labeled CF terminals were seen in both the superficial Purkinje cell (PC) layer (normally positioned PCs) and around PCs in the granular layer and central masses (ectopic PCs). The pattern of labeling is suggestive of orthogonal organization, in that vertical columns of cells are labeled. This is especially apparent in the medial PC group, where at least three bands are identified. Within an orthogonal band, CF terminals are seen around both superficial and deep Purkinje cells. Our data indicate that olivocerebellar topography is generally similar in reeler and normal mice despite severe abnormalities in target cell position in the reeler. The medial cerebellar region receives input from the caudal two-fifths of the medial accessory olive (MAO). The intermediate PC cluster receives input from more rostral portions of all three olivary divisions (MAO, principal olive [PO] and dorsal accessory olive [DAO] ), while rostral portions of MAO and PO project to the lateral cerebellum. These results indicate that the zonal organization of the olivocerebellar projection in the adult reeler exhibits a pattern generally similar to that seen in normal mice. This suggests that an afferent system can develop a normal organization despite having ectopic targets.