title: Reinnervation of late postnatal Purkinje cells by climbing fibers: neosynaptogenesis without transient multi-innervation.
abstract: Synaptic partner selection and refinement of projections are important in the development of precise and functional neuronal connections. We investigated the formation of new synaptic connections in a relatively mature system to test whether developmental events can be recapitulated at later stages (i.e., after the mature synaptic organization has been established), using a model of postlesional reinnervation in the olivo-cerebellar pathway. During the development of this pathway, synaptic connections between climbing fibers (CFs) and Purkinje cells (PCs) are diffuse and redundant before synapse elimination refines the pattern. The regression of CFs during the first 2 postnatal weeks in the rat leads to mono-innervation of each PC. After unilateral transection of the rat olivo-cerebellar pathway and intracerebellar injection of BDNF 24 h after lesion, axons from the remaining inferior olive can sprout into the deafferented hemicerebellum and establish new contacts with denervated PCs at later developmental stages. We found that these contacts are first established on somatic thorns before the CFs translocate to the PC dendrites, recapitulating the morphological steps of normal CF-PC synaptogenesis, but on a relatively mature PC. However, electrophysiology of PC reinnervation by transcommissural CFs in these animals showed that each PC is reinnervated by only one CF. This mono-innervation contrasts with the reinnervation of grafted immature PCs in the same cerebellum. Our results provide evidence that relatively mature PCs do not receive several olivary afferents during late reinnervation, suggesting a critical role of the target cell state in the control of CF-PC synaptogenesis. Thus, synapse exuberance and subsequent elimination are not a prerequisite to reach a mature relationship between synaptic partners.
authors.affiliation: Université Pierre et Marie Curie-Paris, Unité Mixte de Recherche 7102-Neurobiologie des Processus Adaptatifs, F-75005 Paris, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Letellier
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bailly
authors.forename: Valérie
authors.initials: V
authors.lastname: Demais
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Sherrard
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Ann M
authors.initials: AM
authors.lastname: Lohof
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development; D005260:Female; D008297:Male; D011689:Purkinje Cells / Q000166:cytology* / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D013997:Time Factors