Architectonic and hodological organization of the cerebellum in reeler mutant mice.

The architectonic and hodologic organization of the reeler cerebellum has been studied by means of immunohistochemistry, general cell and fiber stains and by horseradish peroxidase and autoradiographic tracing methods. Malposition of Purkinje cells, which varies in degree, is the most salient architectonic anomaly of the mutant cerebellum. Mapping the distribution of Purkinje cells is facilitated by a monoclonal antibody which selectively stains neurons of this class in the cerebellum. Although some Purkinje cells form a normal monolayer, most lie in heterotopic positions within or below the granule cell layer. The major contingent is segregated in subcortical masses in the depths of the cerebellum. Fiber bundles continuous with the cerebellar peduncles run in septa between the subcortical Purkinje cell masses. The distribution of Purkinje cell masses as well as the roof nuclei and areas of normal cortex and fiber bundles are identical from animal to animal. These consistent architectonic variations serve to partition the reeler cerebellum into 7 sagittally oriented compartments: one medial, two intermediate, two lateral and two additional lateral lobular appendages which may correspond to paraflocculus and/or flocculus of the normal cerebellum. The topography of the reeler olivocerebellar, or climbing fiber, system is normal in that the caudal-to-rostral axis of the olivary complex maps onto the medial-to-lateral axis of the contralateral hemicerebellum. The climbing fiber projection in reeler, like that of the normal animal, appears to be organized in parasagittal strips. In the mutant, mossy fibers from the pons and spinal cord project respectively to the lateral and medial cerebellar fields, and overlap in the intermediate compartment. They thus invest different and to a large extent complementary cerebellar territories, which approximate the architectonic divisions. This segregation of the two principal mossy fiber systems is not so marked in the normal cerebellum. In terms of laminar distribution, the pontine projection is distributed principally to the granule cell stratum in the mutant. The reeler spinocerebellar afferents, by contrast, project not only to the granule cell layer but also to the heterotopic Purkinje cells. The present observations suggest that the primary defect in the reeler cerebellum is malposition of Purkinje cells. As appears to be the case during development of the forebrain in reeler, the mutation may affect the terminal phase of migration of Purkinje cells in the cerebellum.(ABSTRACT TRUNCATED AT 400 WORDS)