Anterograde transsynaptic degeneration in the deep cerebellar nuclei of Purkinje cell degeneration (pcd) mutant mice.

The genetically-determined loss of Purkinje cells (PCs) in 'Purkinje cell degeneration' (pcd) mutant mice results in the loss of presynaptic afferents to the deep cerebellar nuclei (DCN). This deafferentation takes place between postnatal day (P)17 and P45, i.e. after the maturation of cerebellar circuitry. We examined the DCN of normal and pcd mutant mice by quantitative light microscopic methods to determine whether neuronal atrophy or loss in the DCN take place during and after the loss of their input from the PCs. Neuronal diameters in control mice were 16.4 +/- 0.72 microns (mean +/- S.D.) at P23 and 15.6 +/- 0.64 microns at P300. The respective values in pcd mutant mice were 15.7 +/- 0.58 microns and 13.5 +/- 0.24 microns. Diameters in 300-day-old mutants were significantly smaller than those in both age-matched controls and 23-day-old mutants (P less than 0.001). Neuronal populations in the DCN of control mice were 10,167 +/- 949 at P23 and 10,429 +/- 728 at P300. The respective values in mutants were 9,436 +/- 1,366 and 7,424 +/- 1,324. There was a significant difference of 29% [95% confidence limits: 9-45%] between 300-day-old mutants and age-matched controls (P less than 0.01), and a significant loss of 21% [95% confidence limits: 4-36%] in 300-day-old mutants with respect to 23-day-old mutants (P less than 0.05). The total volume of the DCN was 22% less in 300-day-old mutants in relation to 23-day-old mutants (P less than 0.05). These findings support the idea that the stability of DCN neurons in the mature cerebellum depends in part on the synaptic input from PCs.