Regressive modifications of climbing fibres following Purkinje cell degeneration in the cerebellar cortex of the adult rat.

The role of postsynaptic neurons in the maintenance of adult terminal axon arbours was investigated in the rat olivocerebellar system. The degeneration of Purkinje cells, the main target of olivary axons in the cerebellar cortex, was obtained by intraparenchymal application of kainate. The structural features of target-deprived climbing fibres, visualized by Phaseolus vulgaris leucoagglutinin tracing, were examined from two days to six months after the lesion. Following the degeneration of its Purkinje cell, the climbing fibre underwent remarkable regressive modifications involving the disappearance of most of the terminal arborization. Never the less, atrophic arbours still spanned through the molecular layer six months after the lesion. Morphometric evaluations showed that, one week after kainate application, total arbour length was already reduced to 52% of control, whereas the number of branches and of varicosities had both dropped around 40%. This retraction process progressed in the following stages to reach its maximum at about one month after the lesion, when total length was 30% of control and only 10% of branches and varicosities were still present. Only a slight tendency to a further decrease of the values could be detected at longer survival times. Branching pattern analysis revealed that such regressive phenomena mainly involved the distal compartment of the climbing fibres, the one made of fine varicose branchlets, while sparing the proximal thick branches. In addition, the whole process appeared to follow some rather strict guiding principles leading to an ordered branch retraction, from the periphery of the arbour inwards. Finally, in order to rule out the possibility that the observed changes could be due to a direct action of kainate on climbing fibres, we designed an alternative method of killing Purkinje cells by intraparenchymal injection of propidium iodide. The structural features of climbing fibres deprived of their target by such a procedure were very similar to those shown by arbours from time-matched kainate-lesioned animals at both qualitative and quantitative levels. Our results show that target deprivation induces remarkable structural modifications in the climbing fibre, leading to the retraction of most of the arbour. Never the less, the integrity of the Purkinje cell is not necessary for the maintenance of the whole arborization since its proximal compartment is maintained in the molecular layer for several months after target degeneration. It is proposed that the Purkinje cell, most likely by acting through a contact factor, directly controls the formation and the maintenance of the distal climbing fibre branches with their varicosities, which represent the presynaptic compartment of the axonal arbour.