The olivocerebellar projection in normal (+/+), heterozygous weaver (wv/+), and homozygous weaver (wv/wv) mutant mice: comparison of terminal pattern and topographic organization.

Abstract

Olivocerebellar organization and topography were analyzed in adult normal (+/+), heterozygous weaver (wv/+), and homozygous weaver (wv/wv) mutant mice. The two genotypes (wv/+ and wv/wv) of the weaver mutant present a gradation of abnormal cerebellar morphology. Purkinje cell (PC) ectopia ranges from mild (wv/+) to moderate (wv/wv), and regional PC loss is also graded in the two types. To determine olivocerebellar organization and topography, tritiated amino acids were placed into different regions of the inferior olivary complex (IO) in normal, heterozygous, and homozygous weaver mice. Despite some PC loss and ectopia, olivocerebellar fiber (OCF) terminals in both homozygous and heterozygous weaver mice have an orthogonal distribution and topography similar to that seen in normal mice. Differences in OCF termination, such as an increased density of OCF terminal label in the lower portion of the molecular layer, the PC, and granule cell layers, are seen in homozygous weaver mice. In some heterozygous weaver and normal cases, multiple injections labeling most IO cells on one side of the IO resulted in continuous OCF terminal labeling in many regions of the contralateral cerebellar cortex, suggesting that all PCs receive OCF input. Retrograde analysis involving injections of horseradish peroxidase conjugated to wheat germ agglutinin into different mediolateral cerebellar regions in homozygous weaver mice further demonstrates a generally normal olivocerebellar topography.