A qualitative and quantitative light microscopic study of the inferior olivary complex of normal, reeler, and weaver mutant mice

Abstract

In the normal mouse (+/+; +/rl) cerebellar Purkinje cells (PCs) are aligned in a monolayer and provide the main targets for incoming olivocerebellar climbing fibers (CF). In the neurological mutants, homozygous reeler (rl/rl), homozygous weaver (wv/wv) and heterozygous weaver (wv/+), cerebellar abnormalities exist in which many PCs are either missing or displaced. Therefore, it is of interest to determine if the inferior olivary complex (IO) in these mutants is also abnormal. This report concerns results obtained from a light microscopic study of the inferior olivary complex. Counts of IO cells revealed apparent differences in the IO in homozygous reeler when compared to normal littermates. Whereas in the normal mouse there are approximately 37,000 IO cells and clearly defined olivary subdivisions, the IO of the homozygous reeler has a 22.6% reduction in IO cells (mean = 28,770) and indistinct borders between the major olivary subdivisions. With regard to the heterozygous and homozygous weaver, surprisingly the IO morphology and cell numbers are similar to that of the wildtype mouse even though the animals have only 86% (wv/+, mean = 158,155) and 72% (wv/wv, mean = 131,882), respectively, of the normal numbers of PCs (+/+, mean = 183,857). Purkinje cell counts revealed that the midline vermal region is the most affected area in the cerebellum in wv/+ and wv/wv whereas counts in the lateral hemisphere are near normal. The PC/IO ratio in the homozygous weaver is approximately 3:1 as compared to 5:1 in the wildtype mouse. Recent electrophysiological findings in wv/wv indicate that PCs are multiply innervated by CFs. Since a transient phase of multiple innervation is normal in the immature rat, the situation in the adult homozygous weaver may represent a retention of this immature state. A factor which may play a role in this is the loss of parallel fiber (PF)-PC synapses resulting from massive postnatal granule cell death. An hypothesis suggesting an intrinsic PC time-dependent mutant gene effect is presented to account for the differences in the loss of Purkinje cells between wv/wv and wv/+ and between different regions of the cerebellum.