IGF-I induces neonatal climbing-fibre plasticity in the mature rat cerebellum

Abstract

Following unilateral transection (pedunculotomy) of the neonatal rat olivocerebellar pathway, the remaining inferior olive reinnervates the denervated hemicerebellum with correct topography. The critical period for this transcommissural reinnervation closes between postnatal days 7 and 10 but can be extended by injection of growth factors. Whether growth factor treatment can extend developmental plasticity into a mature, myelinated milieu remains unknown. Rats aged 11-30 days, underwent unilateral pedunculotomy followed 24 h later by injection of insulin-like growth factor 1 (IGF-1) into the denervated cerebellum. In all animals, IGF-1 induced transcommissural olivocerebellar reinnervation, which displayed organisation consistent with normal olivocerebellar topography even following pedunculotomy up to day 20. Thus IGF-1 can reproduce developmental neuroplasticity to promote appropriate target reinnervation in a mature myelinated environment.