SPATIAL AND TEMPORAL PATTERN OF PURKINJE-CELL DEGENERATION IN SHAKER MUTANT RATS WITH HEREDITARY CEREBELLAR-ATAXIA

Temporal-spatial patterns of surviving Purkinje cells were studied qua ntitatively in a rat mutant (shaker) with differential hereditary cere bellar ataxia and Purkinje cell degeneration. Shaker rat mutants are c haracterized behaviorally as mild if they are ataxic or as strong if t hey have ataxia and tremor. Purkinje cells degenerate in both mild and strong shaker mutants, but the temporal and spatial patterns of cell death are strikingly different. In mild shaker mutants, Purkinje cell death is temporally restricted, with 31-46% of the Purkinje cells in l obules I-IX dying by 3 months of age. Very few Purkinje cells degenera te after this age. Purkinje cell death is spatially random. In lobules I-IX, every second, third, or fourth Purkinje cell degenerates. Purki nje cells in lobule X do not degenerate. In strong shaker mutants, Pur kinje cell degeneration is temporally protracted and spatially restric ted. By 3 months of age, most Purkinje cells in lobules I-VIa, -b, and -d have degenerated. Numerous Purkinje cells in the paravermis of lob ules VIIb-VIII have also degenerated. Surviving Purkinje cells in the vermis and lateral hemisphere of lobules VIIb-VIII are aligned in para sagittally oriented stripes or transversely oriented bands. Purkinje c ells continue to degenerate in localized areas of the posterior lobe s uch that, by 18 months of age, surviving Purkinje cells are limited pr imarily to lobules Vlc, VIIa, IXd, and X. Quantitative analysis indica tes that none of the Purkinje cells in these lobules degenerate. (C) 1 995 Wiley-Liss, Inc.