Post-lesion transcommissural olivocerebellar reinnervation improves motor function following unilateral pedunculotomy in the neonatal rat

In the adult mammalian central nervous system, reinnervation and recovery from trauma are limited. During development, however, post-lesion plasticity may generate alternate paths providing models to investigate reinnervation and repair. Sometimes, these paths are maladaptive, although the relationship between dysfunction and anatomical abnormality remains unknown. After unilateral transection of the neonatal rat olivocerebellar path (pedunculotomy), axons from the remaining inferior olive reinnervate Purkinje cells in the denervated hemicerebellum with appropriate topography and synaptic function. However, whether this new pathway confers beneficial behavioural effects remains unknown. We studied the behavioural sequelae in rats with and without transcommissural reinnervation using righting and vestibular-drop reflexes, simple locomotion (bridge), complex locomotion (wire) and motor coordination (rotarod) tests. In animals pedunculotomised on day 3 (Px3), which develop olivocerebellar reinnervation, dynamic postural adjustments and complex motor skills develop normally, whereas simple gait is broad-based and slightly delayed. In contrast, Px I I animals, which do not develop reinnervation, have delayed maturation of postural reflexes, gait and complex locomotor skills. In addition, when compared to control animals, their performance in locomotory tasks was slower and the complex task impaired. On the rotarod, control and Px3 animals learned to coordinate their gait and walked for longer at 10 and 20 rpm than Px 11 animals. These results show that transcommissural olivocerebellar reinnervation is associated with almost normal motor development and the ability to synchronise gait at slow and moderate speeds, i.e. this reinnervation confers significant behavioural function and is therefore truly compensatory. (c) 2005 Elsevier Inc. All rights reserved.