Cell Interactions Underlying Purkinje Cell Replacement by Neural Grafting in the pcd Mutant Cerebellum

Abstract

ABSTRACT:The results obtained with neuronal grafting in an animal model of heredo-degenerative ataxia (the pcd mutant mouse) have been extremely useful to unmask new aspects of neural plasticity. The grafted embryonic Purkinje cells invade the deficient molecular layer of the host by migrating radially through adult Bergmann fibers. There, they start building their dendritic trees and, by promoting the axonal sprouting of specific adult neuronal population in a timed sequence, they receive appropriate synaptic contacts, starting ten days after grafting. Twenty-one days after grafting, the grafted Purkinje cells have acquired their adult dendritic pattern and synaptic investment. Both the detailed timetable and the nature of the cellular interactions between embryonic and adult neural cells are remarkably similar to those occurring during normal development. These results raise the possibility that embryonic Purkinje cells can induce in adult neural cells a new type of plasticity, that of recreating a permissive microenvironment for the synaptic integration of the grafted neurons, leading to the anatomical restoration of the cortical circuit of the mutant cerebellum. RESUME: Interactions cellulaires qui sous-tendent le remplacement, par greffe neurale, des cellules de Purkinje dans le cervelet de la souris mutante pcd. Les resultats obtenus par greffe neurale dans un modele animal d'ataxie heredo-degenerative (la souris mutante pcd) ont permis de devoiler des aspects nouveaux de la plasticite neurale. Les cellules de Purkinje embryonnaires greffees envahissent la couche moleculaire de l'hote en migrant radialement sur les fibres de Bergmann adultes. Dans cette couche, les neurones greffes commencent a batir leurs arbres dendritiques et, en provoquant la poussee collaterale des axones de populations neuronales specifiques de l'hote, ils vont recevoir des contacts synaptiques appropries, a partir de 10 jours apres transplantation. Vingt et un jours apres transplantation, les cellules de Purkinje greffees ont deja acquis des arbres dendritiques et une synaptologie de type adulte. La chronologie et la nature des interactions entre cellules neurales embryonnaires et adultes sont remarquablement similaires a celles qui ont lieu pendant le developpement normal. Ces resultats incitent a penser que les cellules de Purkinje embryonnaires peuvent induire dans les cellules neurales adulte un type nouveau de placticite : la recreation d'un microenvironnement permissif pour l'integration synaptique des neurones greffes, entrainant la restauration anatomique d'un circuit cortical de la souris mutante.