Neuronal plasticity and formation of new synaptic contacts follow pyramidal lesions and neutralization of Nogo-A: A light and electron microscopic study in the pontine nuclei of adult rats

Regeneration and compensatory sprouting are limited after lesions in the ma ture mammalian central nervous system in contrast to the developing central nervous system (CNS). After neutralization of the growth inhibitor Nogo-A, however, massive sprouting and rearrangements of fiber connections occurre d after unilateral pyramidal tract lesions in adult rats: Corticofugal fibe rs from the lesioned side crossed the midline of the brainstem and innervat ed the contralateral basilar pontine nuclei. To determine whether these new ly sprouted fibers formed synaptic contacts, we analyzed the corticofugal f ibers in the basilar pontine nuclei contralateral to the lesion by light an d electron microscopy 2 weeks after pyramidotomy and treatment with the Nog o-A-inhibiting monoclonal antibody IN-1 (mAb IN-1). The mAb IN-1, but not a control antibody, led to structural changes in the basilar pens ipsilatera l and contralateral to the lesion site. Fibers sprouted across the pontine midline and terminated topographically. They established asymmetric synapti c contacts with the characteristics of normal corticopontine terminals. The se results show that adult CNS fibers are able to sprout and to form new sy naptic contacts after a lesion when a growth-permissive microenvironment is provided. (C) 2001 Wiley-Liss, Inc.