PARTIAL ABLATION OF THE NEONATAL EXTERNAL GRANULAR LAYER DISRUPTS MOSSY FIBER TOPOGRAPHY IN THE ADULT-RAT CEREBELLUM

The spinocerebellar projection in the rat is compartmentalized in an a rray of parasagittal bands of messy fiber terminals. These bands align reproducibly with bands of Purkinje cells that differentially express zebrin II. To investigate whether this alignment is obligatory, Purki nje cell and messy fiber compartmentation has been compared in the rat cerebellum where the cytoarchitecture was contorted by neonatal admin istration of methylazoxymethanol. Methylazoxymethanol ablates many gra nule 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 immuno-cytochemistry nevertheless revealed no fundamental abnormal ity in the Purkinje cell compartments. However, despite the normal Pur kinje cell compartmentation being retained, the spinocerebellar messy fiber-Purkinje cell topography is disrupted by methylazoxymethanol tre atment. The normal precise array of parasagittal messy fiber terminal fields becomes blurred across the lobule, and the normal clear banding is difficult to follow. These data suggest that, despite the early to pography being dependent on the Purkinje cells, the granule cell-messy fiber interactions also regulate the topography of the spinocerebella r projection. (C) 1996 Wiley-Liss, Inc.