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

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.