Compartmentation of the reeler cerebellum: segregation and overlap of spinocerebellar and secondary vestibulocerebellar fibers and their target cells

Abstract

The cerebellum of the reeler mutant mouse has an abnormal organization; its single lobule is composed of a severely hypogranular cortex and a central cerebellar mass (CCM) consisting of Purkinje cell clusters intermixing with the cerebellar nuclei. As such the reeler represents an excellent model in which to examine the effect of the abnormal distribution of cerebellar cells on afferent-target relationships. To this effect we studied the organization of the spinocerebellar and secondary vestibulocerebellar afferent projections in homozygous reeler mice (rl/rl) using anterograde tracing techniques. Spinal cord injections resulted in labeled spinocerebellar mossy fiber rosettes in specific anterior and posterior regions of the cerebellar cortex. Some vestiges of parasagittal organization may be present in the anterior projection area. Within the CCM, labeled fibers appeared to terminate on distinct groups of Purkinje cells. Thus, the spinocerebellar mossy fibers seem to form both normal and heterologous synapses in the reeler cerebellum. Secondary vestibular injections resulted in both retrograde and anterograde labeling. Retrograde labeling was seen in clusters of Purkinje cells and cerebellar nuclear cells; anterograde labeling was distributed in the white matter and in specific regions of the anterior and posterior cortex of the cerebellum. The labeled spinocerebellar and secondary vestibulocerebellar afferents overlapped in the anterior region but in the posterior region the vestibulocerebellar termination area was ventral to the spinocerebellar area. An area devoid of labeled terminals was also observed ventral to the posterior secondary vestibulocerebellar termination field. Using calretinin immunostaining it was determined that this area contains unipolar brush cells, a cell type found primarily in the vestibulocerebellum of normal mice. Our data indicate that despite of the lack of known landmarks (fissures, lobules) the spinocerebellar and vestibulocerebellar afferent projections in the reeler cerebellum do not distribute randomly but have specific target regions, and the position of these regions, relative to each other, appears to be conserved. Two caveats to this were the finding of overlapping terminal fields of these afferents in the anterior region, and a posteroventral region that contains unipolar brush cells yet is devoid of secondary vestibulocerebellar afferents. The distribution of Purkinje cells and cerebellar nuclear cells is not random either; those that give rise to cerebellovestibular efferents form distinct groups within the central cerebellar mass.