Innervation of the adult rat cerebellar hemisphere by fibres from the ipsilateral inferior olive following unilateral neonatal pedunculotomy: an autoradiographic and retrograde fluorescent double-labelling study

Abstract

A left cerebellar pedunculotomy was carried out in neonatal rats of different ages to deprive the left cerebellar hemisphere of its normal climbing fibre input. In control adult animals this is totally crossed and thus arises only from the contralateral (right) inferior olive. After pedunculotomy, only the left inferior olive was intact, the right being degenerated. The remaining olivocerebellar pathway was investigated using anterograde autoradiographic or retrograde fluorescent double-labelling techniques. The anterograde autoradiographic technique showed that, in these animals, the remaining left inferior olive had an aberrant climbing fibre projection which travelled via the intact right inferior cerebellar peduncle to the denervated left hemicerebellum. If the pedunculotomy was carried out at 3 days of age (P3), this aberrant projection closely mirrored the normal pathway to the opposite hemisphere; pedunculotomy at P7 produced a different pattern of projection; while if the operation was done at P10 there was no new projection. True blue (TB) and diamidino yellow (DY) were injected into the denervated (left) and normal (right) cerebellar hemispheres respectively. Retrograde transport of these tracers confirmed both the aberrant ipsilateral projection and the normal crossed projection from neurons in the remaining inferior olive. Most of the ipsilaterally projecting neurons were in the medial accessory olive. As none of them were double-labelled, it was concluded that the new projection is not a collateral of normally projecting olivary neurons, but arises from a separate population of cells. The significance of these findings in relation to earlier work on this system is discussed.

Morphology of single olivocerebellar axons labeled with biotinylated dextran amine in the rat

“…It seems that neurons with bilateral projection, although small in number, are generally present in several subnuclei of the IO, since Brown (1980) and Hrycyshyn (1989) found some in the rostral principal olive and rostral dorsal accessory olive, and we found some in the medial accessory olive. Double-crossing projection of OC axons has been found after cutting the ICP in the newborn period (Angaut et al, 1985;Sherrard et al, 1986). Ipsilateral innervation by some OC axons is transiently formed in young animals, although the pathway is not clear (López-Romá n et al, 1993).…”

Reinnervation of Late Postnatal Purkinje Cells by Climbing Fibers: Neosynaptogenesis without Transient Multi-Innervation

“…Around postnatal day 5 (P5) in the rat, when PCs have short immature den-drites, CFs make perisomatic contacts on the PCs, forming the somatic nest (Ramon y Cajal, 1911). Later, CF terminals move up the growing dendrites and reach the proximal dendritic compartment by P10 -P15 (Larramendi, 1969;Mason et al, 1990;Chedotal and Sotelo, 1993) After unilateral transection of the olivo-cerebellar pathway (pedunculotomy) during the first postnatal week, the axotomized neurons of the inferior olive (IO) degenerate, and new axons arising from the unaffected IO grow through the cerebellar white matter into the denervated hemicerebellum and establish new synapses with PCs (Angaut et al, 1982;Sherrard et al, 1986;Zagrebelsky et al, 1997;Sugihara et al, 2003). During this early postnatal period, neosynaptogenesis involves a transient phase of multiinnervation, indicating that young PCs can be reinnervated by multiple CFs .…”

“…During this early postnatal period, neosynaptogenesis involves a transient phase of multiinnervation, indicating that young PCs can be reinnervated by multiple CFs . After this period of plasticity, no spontaneous reinnervation occurs (Sherrard et al, 1986) but it can be induced by the injection of neurotrophic factors Bower, 2001, 2003).…”

Architecture and development of olivocerebellar circuit topography

“…The olivocerebellar pathway is an excellent example of a system in which regrowth establishes a new pathway. Various groups have used the pedunculotomy approach to stimulate transcommissural olivocerebellar reinnervation to determine the temporal properties of afferent-target interactions during development (Angaut et al, 1985; Sherrard et al, 1986; Zagrebelsky et al, 1997; Sugihara et al, 2003; Dixon et al, 2005; Willson et al, 2007). Following unilateral early postnatal transection of an inferior cerebellar peduncle (which carries the climbing fibers), the contralateral inferior olive degenerates and new axons, arising from the remaining inferior olive, grow into the denervated hemicerebellum (Zagrebelsky et al, 1997).…”