Evidence of spinocerebellar mossy fiber segregation in the juvenile staggerer cerebellum.

Developmental and experimental studies of climbing fiber and mossy fiber connectivity in the cerebellum have suggested that Purkinje cells are the critical organizing elements for connectivity patterns. This hypothesis is supported by evidence that spinocerebellar mossy fiber projections are abnormally diffuse in P25 sg/sg mutant mice in which the differentiation of a reduced number of sg/sg Purkinje cells is blocked due to a cell autonomous defect. However, mossy fiber distribution may be disrupted in sg/sg mutants not because of the Purkinje cell deficits, but because of the death of virtually all granule cells following the 4th postnatal week. To test this hypothesis, we have analyzed the distribution of wheat germ agglutinin-horseradish peroxidase (WGA-HRP)-labeled spinocerebellar mossy fiber terminals in sg/sg mutants at the end of the period of granule cell genesis (postnatal day [P] 12-P13) and before massive granule cell death (P16). Two percent WGA-HRP was injected into the lower thoracic/upper lumbar region of the spinal cord of eight homozygous sg/sg mutants (P12-P16) and five controls (+/sg and +/+). We have found that spinocerebellar mossy fibers segregate into distinct terminal fields in the anterior cerebellar lobules of P12 to P16 sg/sg mutants, although the medial-lateral distribution of spinocerebellar mossy fiber projections is different from controls. The results from this study and previous analysis of sg/sg mutants support the hypothesis that topographic cues are expressed in the early postnatal staggerer mutant, but mossy fiber terminals become disorganized or retract as granule cells die in the older staggerer mutant. J. Comp. Neurol. 378:354-362, 1997.