Development of Longitudinal Patterns in the Cerebellar Cortex

Summary

Cerebellar Purkinje cells in the adult are arranged in longitudinal zones which differ in their connections and their biochemical properties. During early development this zonal pattern is preceded by a clustering of Purkinje cells. The topographical relationship of these clusters to the cerebellar and vestibular nuclei is similar to the cortico-nuclear relations of the adult zones. Both the adult and the embryological pattern can be considered the result of the interdigitation of two sets of Purkinje cells with different connections.

It has become increasingly clear that the Purkinje cells of the cerebellar cortex are arranged in a series of parallel longitudinal zones which differ in their efferent, corticonuclear and afferent, climbing fiber connections and in their biochemical properties. Originally this zonal pattern was recognized from the clustering of the Purkinje cell axons and the olivocerebellar climbing fiber afferents in discrete compartments of the white matter^16,17. These compartments can be visualized with the Häggqvist myelin stain and with staining for acetylcholinesterase (AChE, Fig. 1K). The borders between the compartments contain a higher concentration of thin fibers which stain rather strongly for AChE^4,22. There is no explanation for the preferential staining of these fibers for AChE. Cholinergic transmission is limited to certain mossy fiber systems and is not distributed in this pattern⁶.

The connections of the different Purkinje cell zones are known in some detail. The diagram of Fig. lA,C,F illustrates the principle that Purkinje cells which establish efferent connections with the rostral fastigial, the lateral vestibular, the anterior interposed (i.e. emboliform) and the rostral dentate nucleus, alternate with zones where the Purkinje cells project to the caudal fastigial and posterior interposed (globose) nuclei. These two sets of zones receive their climbing fibers from the dorsal accessory olive with the dorsal leaf of the principal olive and from the ventral leaf and the medial accessory olive respectively^19,22. The interdigitation of two sets of Purkinje cells with different connections therefore, seems to be the most simple way to describe this pattern (Fig. lB,D,E).

It should be appreciated that the zonal organization of the cerebellum is a highly constant one in different mammalian species. This has been well documented for the zonation of the anterior vermis. Purkinje cells with projections to the vestibular nuclei are located in two strips. One occupies the lateral part of the vermis and corresponds to the B zone projecting to Deiters′ nucleus, the other is situated along the lateral border of the A-zone. The latter (A2) zone projects both to the fastigial nucleus and the medial vestibular nucleus. The B and A2 zones are separated by the wedge-shaped X zone which contains Purkinje cells projecting to the fastigial and posterior interposed nuclei¹⁸. The same intricate pattern is found in different mammals²¹ , including rodents (Fig. U) and primates (Fig. II).

The distribution of several enzymes, receptors and Purkinje cell-specific markers in the cerebellar molecular layer follows a zonal pattern. One group of these substances is present at the midline and in six or seven parasagittal strips. These substances have been mainly studied in rodents. They include the enzyme 5′-nucleotidase¹⁴ which is present in Purkinje cell dendrites” and/or radial fibers of Bergmann glia³ . A monoclonal antibody directed against a Purkinje cell specific protein (mabQH3 or antizebrin² is limited to a population of Purkinje cells, where it is expressed by the entire neuron, including dendrites and axon. The zonal pattern of zebrin-positive Purkinje cells exactly corresponds to the distribution of 5′-nucleotidase¹ . Other monoclonal antibodies, such as 192 IgG specific for the rat nerve growth factor receptor, display the same compartmentalization¹⁵ .