EVIDENCE OF SPINOCEREBELLAR MOSSY FIBER SEGREGATION IN THE JUVENILE STAGGERER CEREBELLUM

Developmental and experimental studies of climbing fiber and messy fib er connectivity in the cerebellum have suggested that Purkinje cells a re the critical organizing elements for connectivity patterns. This hy pothesis is supported by evidence that spinocerebellar messy fiber pro jections 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, messy fiber distribution ma y be disrupted in sg/sg mutants not because of the Purkinje cell defic its, 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 messy fiber terminals in sg/sg mutants at th e 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 i njected into the lower thoracic/upper lumbar region of the spinal cord of eight homozygous sg/sg mutants (P12-P16) and five controls (+/sg a nd +/+). We have found that spinocerebellar messy fibers segregate int o distinct terminal fields in the anterior cerebellar lobules of P12 t o P16 sg/sg mutants, although the medial-lateral distribution of spino cerebellar messy fiber projections is different from controls. The res ults from this study and previous analysis of sg/sg mutants support th e hypothesis that topographic cues are expressed in the early postnata l staggerer mutant, but messy fiber terminals become disorganized or r etract as granule cells die in the older staggerer mutant. (C) 1997 Wi ley-Liss, Inc.