Olivocerebellar fiber maturation in normal and lurcher mutant mice: Defective development in lurcher

Abstract

Olivocerebellar fiber maturation was examined in normal and lurcher mutant mice between postnatal day 5 (P5) and P15, using the anterograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) from the inferior olive. Immunocytochemistry for the Purkinje cell marker PEP-19 was used to demonstrate Purkinje cell development in the same material. In mutant and normal animals, a regional developmental variation is observed such that, when compared at a given age, cortex lining the vermal fissures appears developmentally advanced over cortex in the cerebellar hemispheres. In the primary fissure of the normal animals, the first recognizable Purkinje cell dendrites appear on P6, and the olivocerebellar fibers first enter the climbing stage of their development on P9. In lurcher animals Purkinje cell development proceeds on this schedule, but olivocerebellar fibers are never observed to enter the molecular layer. These afferents maintain dense perisomatic nests around Purkinje cells, even in P13-15 lurchers. Examination of P14 lurchers by transmission electron microscopy indicates that the olivocerebellar fibers form synapses on Purkinje cell somatic spines and that the basket cell axons fail to form their typical perisomal nests around Purkinje cells. In addition, parallel fibers can be observed to synapse on dendritic spines on the Purkinje cell primary dendrites. We interpret these results as indicating a recognition defect between olivocerebellar fibers and Purkinje cell dendrites. An analysis of this defect in lurcher may reveal how the normal transformation of olivocerebellar fibers, from perisomal to dendritic terminals, is achieved.