Developmental neural plasticity and its cognitive benefits: olivocerebellar reinnervation compensates for spatial function in the cerebellum.
Résumé
The adult mammalian central nervous system displays limited reinnervation and recovery from trauma. However, during development, post-lesion plasticity may generate alternative paths, thus providing models to investigate reinnervation and repair. After unilateral transection of the neonatal rat olivocerebellar path (pedunculotomy), axons from the remaining inferior olive reinnervate the denervated hemicerebellum. Unfortunately, reinnervation to the cerebellar hemisphere is incomplete; therefore, its capacity to mediate hemispheric function (navigation) is unknown. We studied sensorimotor control and spatial cognition of rats with and without transcommissural reinnervation using simple (bridge and ladder) and complex (wire) locomotion tests and the Morris water maze (hidden, probe and cued paradigms). Although pedunculotomized animals completed locomotory tasks more slowly than controls, all groups performed equally in the cued maze, indicating that lesioned animals could orientate to and reach the platform. In animals pedunculotomized on day 3 (Px3), which develop olivocerebellar reinnervation, final spatial knowledge was as good as controls, although they learned more erratically, failing to retain all information from one day to the next. By contrast, animals pedunculotomized on day 11 (Px11), which do not develop reinnervation, did not learn the task, taking less direct routes and more time to reach the platform than controls. In the probe test, control and Px3, but not Px11, animals swam directly to the remembered location. Furthermore, the amount of transcommissural reinnervation to the denervated hemisphere correlated directly with spatial performance. These results show that transcommissural olivocerebellar reinnervation is associated with spatial learning, i.e. even partial circuit repair confers significant functional benefit.