Development of the rodent cerebellum and synaptic re-formation of donor climbing terminals on spines of the host Purkinje dendrites after chemical deafferentation.

Reinnervation of host Purkinje cells by donor climbing fibers was observed in the following experiments. Medullary primordial tissue (from E14-E16) containing the inferior olive was grafted into a host rat cerebellum, in which the inferior olivary complex and climbing fibers had been destroyed by intraperitoneal injection of 3-acetylpyridine (3-AP). After 3 weeks, immature as well as mature types of climbing fiber terminals bearing packed round vesicles were found that had established synaptic contacts on dendritic spines of the host Purkinje cells. Quantitative analysis at the ultrastructural level has been carried out. The main results are as follows. (1) The number of preterminals that formed synaptic contacts with spines of the host Purkinje dendrites in the transplanted material increased by 3.4-fold compared to the control (3-AP-treated non-grafted material). (2) The number of mature climbing-type preterminals increased from 0.3-0.9% to 5% after grafting (cf. 22% in normal brain tissue), and the number of immature climbing-type preterminals also increased from 2-10% (control) to 20% after grafting. These changes were statistically significant (P less than 0.01). (3) The number of parallel-type preterminals increased from 13% (control) to 27% after grafting, which was also statistically significant (P less than 0.01). Thus, it appears that the donor climbing fibers grow and develop to find unoccupied spines on the host Purkinje dendrites and establish synaptic contacts, and also that the host parallel fibers may generate axonal sprouts to search their new targets and ultimately to form synaptic contacts with unoccupied spines. In the process of re-modeling the brain, competition for targets is likely to occur between the two kinds of axonal processes, i.e. the donor climbing fibers and the host parallel fibers.