Developmental studies of the inferior olivary nucleus in staggerer mutant mice.

The neurological mutation, staggerer, causes a severe disruption in the integrity of the olivo-cerebellar circuitry. The primary site of action is the Purkinje cell population which is reduced in cell number, with cells that are atrophic in dendritic structure, small in size and ectopic in position. This primary defect has a cascade effect on the Purkinje cell-afferent populations, leading to the target-related cell death of virtually all of the cerebellar granule cells and the majority of the neurons in the inferior olive. As part of our ongoing study of the cell-cell interactions in the cerebellar circuitry, we have studied the inferior olive of the staggerer mutant from birth to adulthood. We find that the reduction in olive neuron number does not occur until after birth in the mutants. On the day of birth, the number of cells is indistinguishable in mutants and in wild type. Similarly, we find that the four principal subnuclei of the olive are well defined at birth, but regress to a state of poor resolution during the first 3 postnatal weeks. Finally, Golgi impregnations reveal that of the two morphological classes of inferior olive neurons, only one class--the Type II or complex dendritic type survive in the mutant. These results are discussed in terms of their implications for the cell--cell interactions in the developing olivocerebellar circuit.