Partial ablation of the neonatal external granular layer disrupts mossy fiber topography in the adult rat cerebellum

Abstract

The spinocerebellar projection in the rat is compartmentalized in an array of parasagittal bands of mossy fiber terminals. These bands align reproducibly with bands of Purkinje cells that differentially express zebrin II. To investigate whether this alignment is obligatory, Purkinje cell and mossy fiber compartmentation has been compared in the rat cerebellum where the cytoarchitecture was contorted by neonatal administration of methylazoxymethanol. Methylazoxymethanol ablates many granule cell precursors, leaving a much reduced external granular layer, and adult rats that received a single methylazoxymethanol injection at birth showed varying degrees of abnormal cerebellar foliation. Zebrin II immunocytochemistry nevertheless revealed no fundamental abnormality in the Purkinje cell compartments. However, despite the normal Purkinje cell compartmentation being retained, the spinocerebellar mossy fiber-Purkinje cell topography is disrupted by methylazoxymethanol treatment. The normal precise array of parasagittal mossy fiber terminal fields becomes blurred across the lobule, and the normal clear banding is difficult to follow. These data suggest that, despite the early topography being dependent on the Purkinje cells, the granule cell-mossy fiber interactions also regulate the topography of the spinocerebellar projection.