Cerebellum (2012) 11:246–258 253 Fig. 4 Calbindin D 28K staining of sagittal cerebellar sections of Cacna1a Purkinje cell-specific knockout mice at different ages. a Calbindin staining reveals normal foliation of the cerebellum at P30 in PCα1KO mice. Purkinje cells are organized in regular rows with no evidence of abnormal morphology. b Purkinje cell loss, particularly in the anterior lobes of PCα1KO mice at P60. Abnormalities in Purkinje cell morphology, such as axonal swellings (arrowheads in inset), can be seen. c Progressive Purkinje cell loss in PCα1KO mice at P100 is now also more prominent in posterior lobes. Axonal swellings are indicated by arrowheads. d Further evidence of the progressive nature of the Purkinje cell degeneration in PCα1KO mice at P200–250. Remaining Purkinje cells often show axonal swelling (arrowhead). Roman numbers indicate the cerebellar lobules. G granule cell layer, PC Purkinje cell layer, M molecular layer, WM white matter. e Purkinje cell degeneration in different cerebellar lobules of P200–250 PCα1KO mice. Quantification of the number of Purkinje cells (PCs) per 100 μm in different lobules in WT (blue; n=3) and PCα1KO (green; n =2) mice. The number of Purkinje cells is significantly decreased in all lobules of PCα1KO mice compared to WT littermates were randomly dispersed throughout the cerebellar cortex (Fig. 5b, e). Still, at this stage we did not observe any secondary cell death of neurons in the granular layer or molecular layer. In contrast at P200–250, both layers in PCα1KO mice contained dying neurons (Fig. 5c, f). Apparently, the loss of their target cells—the Purkinje cells—resulted in loss of part of the granule cells and molecular layer interneurons. Moreover, we observed silver-stained Purkinje cell axons in the white matter surrounding the cerebellar nuclei (Fig. 6). The density of these degenerating fibers is variable throughout the white matter, as can be expected from the alternating density of