title: Post-lesion transcommissural growth of olivary climbing fibres creates functional synaptic microzones.
abstract: In the adult mammalian central nervous system, reinnervation and recovery from trauma is limited. During development, however, postlesion plasticity may generate alternate paths, providing models to investigate reinnervating axon-target interactions. After unilateral transection of the neonatal rat olivocerebellar path, axons from the ipsilateral inferior olive grow into the denervated hemicerebellum and develop climbing fibre (CF)-like arbors on Purkinje cells (PCs). However, the synaptic function and extent of PC reinnervation remain unknown. In adult rats pedunculotomized on postnatal day 3 the morphological and electrophysiological properties of reinnervating olivocerebellar axons were studied, using axonal reconstruction and patch-clamp PC recording of CF-induced synaptic currents. Reinnervated PCs displayed normal CF currents, and the frequency of PC reinnervation decreased with increasing laterality. Reinnervating CF arbors were predominantly normal but 6% branched within the molecular layer forming smaller secondary arbors. CFs arose from transcommissural olivary axons, which branched extensively near their target PCs to produce on average 36 CFs, which is six times more than normal. Axons terminating in the hemisphere developed more CFs than those terminating in the vermis. However, the precise parasagittal microzone organization was preserved. Transcommissural axons also branched, although to a lesser extent, to the deep cerebellar nuclei and terminated in a distribution indicative of the olivo-cortico-nuclear circuit. These results show that reinnervating olivocerebellar axons are highly plastic in the cerebellum, compensating anatomically and functionally for early postnatal denervation, and that this reparation obeys precise topographic constraints although axonal plasticity is modified by target (PC or deep nuclear neurons) interactions.
authors.affiliation: Department of Systems Neurophysiology, Tokyo Medical and Dental University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Izumi
authors.initials: I
authors.lastname: Sugihara
authors.forename: Ann M
authors.initials: AM
authors.lastname: Lohof
authors.forename: Mathieu
authors.initials: M
authors.lastname: Letellier
authors.forename: Jean
authors.initials: J
authors.lastname: Mariani
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Sherrard
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000473:pathology / Q000502:physiology; D001710:Biotin / Q000031:analogs & derivatives* / Q000378:metabolism; D002531:Cerebellum / Q000473:pathology / Q000503:physiopathology*; D003714:Denervation / Q000379:methods; D003911:Dextrans / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D008297:Male; D009412:Nerve Fibers / Q000502:physiology*; D009416:Nerve Regeneration / Q000502:physiology*; D009473:Neuronal Plasticity; D009847:Olivary Nucleus / Q000473:pathology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000473:pathology / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
chemical_list: D003911:Dextrans; C076397:biotinylated dextran amine; D001710:Biotin