Spatial learning in rodents requires normal functioning of hippocampal and cortical structures. Recent data suggest that the cerebellum may also be esential. Neurological mutant mice with dysgenesis of the cerebellum provide useful models to examine the effects of abnormal cerebellar function. Mice with one such mutation, Purkinje cell degeneration (pcd), in which Purkinje cells degenerate between the third and fourth postnatal weeks, were evaluated for performance of spatial navigation learning and visual guidance learning in the Morris maze swim-escape task. Unaffected littermates and C57BL/6J mice served as controls. Separate groups of pcd and control mice were tested at 30, 50 and 110 days of age. At all ages, pcd mice had severe deficits in distal-cue (spatial) navigation, failing to decrease path lengths over training and failing to express appropriate spatial biases on probe trials. On the proximal-cue (visual guidance) task, whenever performance differences between groups did occur, they were limited to the initial trials. The ability of the pcd mice to perform the proximal-cue but not the distal-cue task indicates that the massive spatial navigation deficit was not due simply to motor dysfunction. Histological evaluations confirmed that the pcd mutation resulted in Purkinje cell loss without significant depletion of cells in the hippocampal formation. Teese data provide further evidence that the cerebellum is vital for the expression of behavior directed by spatial cognitive processes.

In order to attain a better understanding of the sprouting response of noradrenergic fibers in the central nervous system (CNS), noradrenergic innervation to the cerebellum was observed by the glyoxylic acid method after a variety of manipulations and in a genetic variant of mouse classified as "Purkinje cell degeneration" (pcd/pcd). It has been found that a midbrain lesion in rats at birth will result in a collateral sprouting response of noradrenergic fibers in the cerebellum at 8 weeks, as indicated by the increased number of histofluorescent fibers observed in the molecular layer of the cerebellar cortex. Another procedure, treatment of neonatal rats with nerve growth factor alone appears to produce a temporary stimulation of noradrenergic fiber growth in the cerebellum, as observed by the histofluorescent method, although the innervation at 6 weeks or later is ultimately unchanged from the control group. In contrast, NGF (500 units) given to rats in combination with 6-hydroxydopa (6-OHDOPA) (60 μg/g IP) at 3 days postbirth produces a hyperinnervation of the cerebellum by noradrenergic fibers by 2 weeks of age and until at least 8 weeks of age. A third procedure, locus coeruleus implantation, was generally unsuccessful using the procedures described, since the implant was usually non-viable after several days. In a few instances where histofluorescent nuclei were found within the implant, there was an abundance of histofluorescent fibers within and adjacent to the implant, with fibers appearing to grow into host cerebellum. In the final procedure, it was noted that the density of noradrenergic input to the molecular layer of the cerebellar cortex was markedly increased in a genetic mutant mouse, classified as "Purkinje cell degeneration" (pcd/pcd), which is characterized by the absence of Purkinje cells of the cerebellum in adulthood. However, because of the tissue shrinkage that occurs after loss of Purkinje cells during postnatal development, it is unclear as to whether this observation represents hyperinnervation or a normal complement of fibers in a smaller brain space. The above procedures demonstrate the plasticity of noradrenergic fibers in neonatal cerebellum, a brain region that undergoes considerable postnatal development. The cerebellum is thought to be a good site for studying development/ regeneration/sprouting of noradrenergic fibers in particular, and central axonal processes in general.