Olivary morphology and olivocerebellar topography in adult lurcher mutant mice.

In adult lurcher mice, in which virtually all cerebellar Purkinje cells have degenerated as a direct consequence of mutant gene action, the inferior olivary complex suffers a severe retrograde transneuronal atrophy. Our analysis indicates a 63% cell loss in the lurcher inferior olive, homogeneously distributed between the medial and dorsal accessory, and principal olivary subdivisions. Olivary neurons are reduced in cross-sectional area by 30% in lurcher mice, compared to normal controls. All olivary subdivisions morphologically identifiable in normal mice are also found in the lurcher inferior olive. Analysis of olivocerebellar topography by retrograde transport of lectin-conjugated horseradish peroxidase and fluorogold, in both single and double labeling paradigms, reveals no abnormalities in the general organization of this highly ordered projection. This stability may be based on the initial establishment of the topographic pattern in late embryogenesis or early postnatal periods, prior to the onset of lurcher Purkinje cell degeneration, or, alternatively, the lurcher gene may not alter critical afferent and target characteristics at stages when the topographic relationship is being established. Once established, the olivocerebellar projection is apparently not dependent on the Purkinje cell for long-term maintenance of its general topographic organization.