title: Reinnervation of cerebellar Purkinje cells by climbing fibres surviving a subtotal lesion of the inferior olive in the adult rat. I. Development of new collateral branches and terminal plexuses.
abstract: Cerebellar climbing fibres react by collateral sprouting after subtotal lesions of the inferior olive, and the newly formed branches are able to reinnervate neighbouring denervated Purkinje cells. In the present paper, we used the Phaseolus vulgaris leucoagglutinin (PHA-L) tracing technique to label the climbing fibres and study their plasticity in detail at the light microscopical level. The specific objectives were to study the time course and morphological aspects of their sprouting, to estimate their extent of growth, and to compare the newly formed terminal plexuses with normal climbing fibres. Intraperitoneal injection of 3-acetylpyridine induced degeneration of the majority of the olivary neurones, which terminate as climbing fibres in the cerebellar cortex. Regularly, small numbers of neurones survived in the inferior olive. In the cerebellar cortex scattered surviving climbing fibres were found, which were devoid of any sign of injury. Already 3 days after the lesion, surviving climbing fibres had emitted collateral branches, which elongated for some distance through the molecular layer and ended with a number of varicosities and very fine branchlets. By 7 days, it was possible to recognize new developing arbours which grew in the molecular layer with the same orientation as normal climbing fibres. At longer survival times, extensive terminal arbours had developed and double labelling experiments confirmed that they terminated around the proximal dendrites of Purkinje cells. The newly formed terminal plexuses resembled, in all essential aspects, normal climbing fibres. In addition, from 1 month onward, it was evident that every surviving climbing fibre was able to form several new terminal plexuses reinnervating a number of neighbouring Purkinje cells. The result of this process was the formation of large clusters of newly formed plexuses around the parental arborization. Quantitative estimates indicated that the domain of innervation of single surviving climbing fibres could be increased by more than six times. It is concluded that climbing fibres surviving a subtotal olivary lesion are capable of extensive sprouting, axonal growth, and formation of new terminal plexuses, which resemble normal climbing fibres. Previous electrophysiological evidence indicates that this reinnervation is functional. The high specificity with which sprouting olivary axons reinnervate the proximal Purkinje cell dendrites suggests the existence of precise interactions between the growing fibres and their target. This example of "homotypic" collateral sprouting and reinnervation may thus provide a useful model for the study of nerve-target interactions.
authors.affiliation: Department of Human Anatomy and Physiology, University of Turin, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Rossi
authors.forename: L
authors.initials: L
authors.lastname: Wiklund
authors.forename: J J
authors.initials: JJ
authors.lastname: van der Want
authors.forename: P
authors.initials: P
authors.lastname: Strata
mesh_terms: D000818:Animals; D003714:Denervation; D005260:Female; D008297:Male; D009473:Neuronal Plasticity; D009847:Olivary Nucleus / Q000166:cytology*; D011689:Purkinje Cells / Q000166:cytology* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013569:Synapses / Q000648:ultrastructure