title: Afferent-target interactions during olivocerebellar development: transcommissural reinnervation indicates interdependence of Purkinje cell maturation and climbing fibre synapse elimination.
abstract: We have used a model of postlesional reinnervation to observe the interactions between synaptic partners during neosynaptogenesis to determine how the developmental states of the pre- and postsynaptic cells influence circuit maturation. After unilateral transection of the neonatal rat olivocerebellar pathway (pedunculotomy), axons from the remaining ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF) terminal arbors on Purkinje cells (PCs) at a later stage of development than normal. However, the significance of delayed CF-PC interactions on subsequent circuit maturation remains poorly defined. To examine this question, we recorded CF-induced currents in PCs and analysed PC morphology during the first two postnatal weeks in control animals and following left unilateral inferior cerebellar pedunculotomy on postnatal day (P)3. Our results show that transcommissural olivary axons multiply-reinnervate PCs in the denervated hemisphere over 4 days following pedunculotomy. Each PC received fewer CFs than did age-matched controls and the maximal multi-reinnervation was reached on P7, 2 days later than in controls. Consequently, the onset of CF synapse elimination in reinnervated PCs was delayed, but then proceeded in parallel with controls so that all PCs were monoinnervated by P15. Furthermore, reinnervated PCs had delayed dendritic maturation and subsequent dendritic abnormalities consistent with the role of CF innervation in PC dendritic growth. Thus, within the olivocerebellar system, our data suggest that target neurons depend upon sufficient afferent investment arriving at the correct time for their normal development, and maturation of the target neuron regulates afferent selection and therefore circuit maturation.
authors.affiliation: Laboratoire Développement et Vieillissement du Système Nerveux, UMR 7102 Neurobiologie des Processus Adaptatifs, CNRS et Université Pierre et Marie Curie, Case courrier 14, 9 quai Saint-Bernard, 75005 Paris, France. ann.lohof@snv.jussieu.fr
authors.forename: Ann M
authors.initials: AM
authors.lastname: Lohof
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Sherrard
mesh_terms: D000375:Aging / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology; D002531:Cerebellum / Q000254:growth & development* / Q000502:physiology*; D004594:Electrophysiology; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D009412:Nerve Fibers / Q000502:physiology* / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000502:physiology* / Q000648:ultrastructure; D009847:Olivary Nucleus / Q000254:growth & development* / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure