Morphology of single olivocerebellar axons in the denervation-reinnervation model produced by subtotal lesion of the rat inferior olive.

An olivocerebellar axon branches into about seven climbing fibers (CFs) as well as several non-CF thin collaterals that terminate mainly in the cerebellar nuclei and in the granular layer. Systemic administration of 3-acetylpyridine (3-AP) induces degeneration of inferior olive neurons. A small number of inferior olive neurons survive the 3-AP treatment and grow up to make compensatory reinnervation on nearby Purkinje cells in their CFs. To elucidate the correlation between denervation-reinnervation processes and morphology of the whole axonal arbor, we reconstructed axonal trajectories of inferior olive neurons in the 3-AP-treated rat in the present study. The number of CFs per axon (average and S.D., 1.6±1.1, n=11 axons) was significantly smaller in the 3-AP-treated rat than that in the untreated rat (about seven), indicating that inferior olive neurons that have a smaller number of CFs are more resistant to 3-AP neurotoxity. Predominant growth of CFs, as well as sprouting of thin collaterals in the cerebellar nuclei and in the granular layer, was observed in the 3-AP-treated rat. A CF was larger in size when an axon had one CF than when an axon had multiple CFs. CFs that were much smaller than the normal CF ("small CFs" in contrast to other "large CFs") were occasionally encountered at the end of thin collaterals and may be new CFs formed from non-CF thin collaterals. The results suggest that the capacity of surviving axons to reinnervate is dependent on targets and possibly limited by neuronal metabolism and axonal flow. Crown