Two monoclonal antibodies--anti-zebrin I and anti-HNK-1--have been used to study the compartmentation of the mouse cerebellar cortex. As in other species, the pattern of localization of the Purkinje cell specific antigen zebrin I is confined to a subset of Purkinje cells that are organized into parasagittal bands. The basic pattern consists of two abutting paramedian bands (P1+) and up to three additional vermal bands on either side (P2(+)-P4+). This pattern is altered in the vermal regions of lobules X and VI-VII where all Purkinje cells are immunoreactive. In the hemisphere there are three additional bands present (P5(+)-P7+) plus two shorter bands in the paravermal area (P4b+ and P5a+) that extend from the paramedian lobule through the lobulus simplex. This pattern is very similar, but perhaps not identical, to that previously described for the rat. These results suggest a common mammalian plan for the expression and localization of zebrin I. By using a monoclonal antibody to an epitope associated with HNK-1, we have now identified a novel pattern of compartmentation in mouse cerebellum. The HNK-1 epitope is expressed most notably on Purkinje cells and Golgi cells. The molecular layer immunoreactivity associated with the Purkinje cell dendrites varies in intensity in a systematic and reproducible fashion. This reveals a novel cerebellar compartmentation that is sometimes complementary, sometimes overlapping, to that revealed by anti-zebrin. As a result, it is now possible to subdivide the cerebellar cortex into a still finer mosaic of antigenic patches and bands than was possible by using zebrins alone.

Malformations of the human neocortex are commonly associated with developmental delays, mental retardation, and epilepsy. This study describes a novel neurologically mutant rat exhibiting a forebrain anomaly resembling the human neuronal migration disorder of double cortex. This mutant displays a telencephalic internal structural heterotopia (tish) that is inherited in an autosomal recessive manner. The bilateral heterotopia is prominent below the frontal and parietal neocortices but is rarely observed in temporal neocortex. Neurons in the heterotopia exhibit neocortical-like morphologies and send typical projections to subcortical sites; however, characteristic lamination and radial orientation are disturbed in the heterotopia. The period of neurogenesis during which cells in the heterotopia are generated is the same as in the normotopic neocortex; however, the cells in the heterotopia exhibit a "rim-to-core" neurogenetic pattern rather than the characteristic "inside-out" pattern observed in normotopic neocortex. Similar to the human syndrome of double cortex, some of the animals with the tish phenotype exhibit spontaneous recurrent electrographic and behavioral seizures.The tish rat is a unique neurological mutant that shares several features with a human cortical malformation associated with epilepsy. On the basis of its regional connectivity, histological composition, and period of neurogenesis, the heterotopic region in the tish rat is neocortical in nature. This neurological mutant represents a novel model system for investigating mechanisms of aberrant neocortical development and is likely to provide insights into the cellular and molecular events contributing to seizure development in dysplastic neocortex.

The Purkinje cells of the cerebellar cortex and the cortical afferent and efferent projections are organized into parallel parasagittal zones. The parasagittal organization is clearly revealed by immunocytochemistry with a monoclonal antibody, mabQ113. The mabQ113 antigen is confined to a subset of Purkinje cells that are clustered together to form an elaborate, highly reproducible pattern of bands and patches, interspersed with similar mabQ113- regions. The mabQ113+ territories have been classified into seven parasagittal bands (P1+-P7+) in each hemicerebellum. The degree of correspondence between the compartments revealed by the anterograde labeling of the olivocerebellar projection and by mabQ113 immunocytochemistry has been explored in the adult rat. Horseradish peroxide-wheat germ agglutinin conjugate was injected as an anterograde tracer into the inferior olivary complex. When the injection site did not encompass all the olive, an incomplete, patchy labeling of the molecular layer was seen in the cerebellar cortex. Labeled zones of the molecular layer were interrupted by unlabeled regions to give a pattern of parasagittal cortical bands. The positions of these bands were compared with the distribution of the mabQ113+ antigenic bands as seen on the two adjacent sections. Labeled climbing fibers were found to terminate on both mabQ113+ and mabQ113- Purkinje cell zones. The mabQ113+/mabQ113- boundaries and the bands of climbing fibers seen by using the anterograde tracer typically coincide. The one consistent exception is the midline band of mabQ113+ Purkinje cells, P1+. The normal olivocerebellar projection is exclusively contralateral and the climbing fiber projection to the paramedian vermis splits P1+ down the middle, implying that it consists of two adjacent mabQ113+ bands not separated by mabQ113-territory. It is likely that the climbing fiber projection to the cerebellar cortex and the distribution of the two Purkinje cell phenotypes share a common compartmental organization.

Because of the limited territories of the olivary dendrites and the precise topographic organization of the olivocerebellar system, the different olivary subdivisions generally are considered as separate and distinct functional entities (Oscarsson, 3 980).

We have used the immunohistochemical detection of the Purkinje cell marker cGMP-dependent protein kinase to identify Purkinje neurons in the cerebellum of the reeler mutant mouse. Our quantitative analysis of Purkinje cell number based on this marker indicates that reeler mice possess approximately 82,000 Purkinje cells, slightly less than half the number found in normal mice. Our analysis also shows that 5% of the Purkinje cells in reeler are located in a normal position (between molecular and granular layers), 10% are found in the granular layer, and the remainder form the deep cellular masses characteristic of the reeler cerebellum. The finding of a major Purkinje cell deficit in reeler was surprising in that most investigators consider this mutation to effect cell migration as opposed to cell number. Although we cannot determine whether the Purkinje cell loss in reeler is a primary or secondary gene effect, the possibility that the reeler gene has its effect on migration through a primary effect on neurogenesis or cell survival should be considered.