Direct correlation between Purkinje and granule cell number in the cerebella of lurcher chimeras and wild-type mice

This study quantitatively examines the developmental relationship between Purkinje cell and granule cell neurons in the cerebellum. Lurcher chimeric mice were used as a model system since target size (i.e. the number of Purkinje cells) can be varied genetically and its effect on granule cell number can be examined. The validity of this model is supported by our previous studies showing that the death of all the Purkinje cells in +/Lc mice is a direct effect of Lc gene action while the loss of 90% of the granule cells is a secondary consequence of some defect extrinsic to the granule cells, most likely the Purkinje cell loss. In the present study of 3 +/Lc mice, 4 strains of wild-type mice and 4 lurcher chimeras, the number of granule cells was directly correlated with the number of Purkinje cells. In wild-type mice, there is a constant ratio of about 175 granule cells for each Purkinje cell. These findings provide suggestive evidence that 'numerical matching' occurs between the presynaptic granule cell population and its postsynaptic target, the Purkinje cell. The quantitative relationships revealed in the chimeric animals compared with the non-chimeric values lead us to propose a model in which the number of granule cells is a function of at least two factors: the initial number of Purkinje cells and the length of time each Purkinje cell is present during a 'critical period' of granule cell development.