Ultrastructural analysis of climbing fiber-Purkinje cell synaptogenesis in the rat cerebellum.

Previous reports have described the transient expression of the neuropeptides calcitonin gene-related peptide and neuropeptide Y in selected subsets of rat olivocerebellar compartments during embryonic and postnatal development. Using these neuropeptides as endogenous markers for olivocerebellar fibers, the aim of this electron microscopic analysis was to reveal the synaptogenetic processes occurring between climbing fibers and their target Purkinje cells, from embryonic day 19 to postnatal day 16, the period during which Purkinje cells undergo intense emission and retraction of dendrites, and climbing fibers translocate their synapses along Purkinje cell membrane surfaces. The present findings provide the first direct evidence that climbing fiber synaptogenesis starts on embryonic day 19 and that these first synapses mainly involve the Purkinje cell embryonic dendrite rather than the Purkinje cell soma. At the same age, the presence of unlabeled synapses resembling calcitonin gene-related peptide-labeled synapses in the Purkinje cell plate makes it possible to conclude that climbing fibers form a major synaptic investment on embryonic Purkinje cells, a finding that strongly supports the hypothesis of an early differentiating role of climbing fibers on cerebellar development. Furthermore, during the period of intense dendritic remodeling of Purkinje cells, 'myelin figures' were often detected in Purkinje cell dendrites suggesting that they may at least in part represent real ultrastructural markers of membrane turnover that identifies the sites where Purkinje cell dendritic rearrangement is taking place. Finally the finding that the climbing fiber terminals apposed to degenerating dendrites did not generally show signs of degeneration leads us to suggests that climbing fiber translocation from a perisomatic to a dendritic location may be driven by the Purkinje cell dendritic remodeling.