Virtually all cerebellar Purkinje cells degenerate in 'Purkinje cell degeneration' (pcd) mutant mice between postnatal day (P) 17 and P45. The inferior olivary complex (IOC) in these mutants undergoes atrophy subsequent to the deprivation of its major cortical target; the number of IOC neurones declines by 18% by P23 and by 49% by P300. In the present study we used control (+/?) and mutant (pcd/pcd) mice that were 14-15 months old to determine whether any further cell loss is observed in the pcd IOC after P300. Nerve cell counts were obtained from serial paraffin sections of the medulla oblongata. The corrected estimate of neurone number in the left IOC of control mice was 12,785±794 cells (mean±SD, n=5); in pcd mutants that number was 6,722±535 (n=5). The 47% difference between control and mutant mice was highly significant (p<0.001). The perikarya of surviving IOC neurones were atrophic. Compared to P17 mutants, pcd homozygotes manifest a 50% cell loss by P428-P446, which does not practically differ from the deficit found on P300. These results suggest that, once a critical neuronal mass degenerates in the IOC of pcd mutants, the remaining neurones become stabilised and no further loss is observed even at an advanced age. The observation that only 50% of neurones degenerate, whereas the remaining 50% become atrophic in the IOC of pcd mutants, along with the fact that the pcd gene is known to be responsible for a 90%-99% loss of its primary CNS targets and not for cell atrophy, favour the contention that the IOC atrophy is transsynaptic. It is possible that surviving IOC neurones are sustained through synaptic connexions of climbing fibre collaterals with cortical interneurones or with neurones of the deep cerebellar nuclei or both.
- Inferior olivary complex
- Neurological mutant mice
- Neurone number
- Purkinje cell degeneration' (pcd)
ASJC Scopus subject areas
- Pathology and Forensic Medicine
- Clinical Neurology