6-OHDA-induced ectopia of external granule cells in the subarachnoid space covering the cerebellum

The present report describes the genesis, development and topographical distribution of ectopic cells of the external granular layer in the subarachnoid space covering the rat cerebellum. Following one intracisternal injection to newborn rats of 100 micrograms 6-hydroxydopamine (6-OHDA), the meningeal cells degenerate and are removed by phagocytosis within 24 h post injection (p.i.), leaving the cerebellar cortex without a pia-arachnoid cover. Defects appear in the basal lamina investing the cerebellar cortex 3 to 5 days p.i., and both external granule cells and 'sprouts' from Bergmann-glia endfeet grow into the subarachnoid space. The latter form large, flat glial lamellae and cover extensive areas of the denuded cerebellar surface, although they do not form a glial scar over the exposed neuropil of the cerebellar cortex. The numbers of ectopic external granule cells increase within the subarachnoid space both by proliferation and a continuous efflux of cells from the cerebellar cortex. They migrate, aggregate, and ultimately develop into granule, stellate and basket cells, the morphology of which is indistinguishable from their counterparts in situ; they make specific afferent and efferent connections, both among themselves and with the underlying cerebellar cortex and brainstem. The distribution of ectopic external granule cells and their derivatives is restricted to the anterior vermal fissures and the vermal-hemispheric junctions. The present results indicate that external granule cells and their derivatives are capable of both differentiating normally and surviving in the subarachnoid space if they become associated with glial cells and establish synaptic connections.