Abstract

The olivocerebellar system is characterised by a precise topographical organisation, in which distinct subsets of inferior olivary axons project to neurochemically heterogeneous Purkinje cell subpopulations, arranged into parasagittally oriented compartments in the cerebellar cortex. Adult climbing fibres and Purkinje cells are linked by a one-to-one relationship, which is established during postnatal development after a transitory phase of multiple climbing fibre innervation. The elimination of redundant climbing fibre synapses is thought to be regulated by granule cell-mediated activity-dependent processes. In order to assess whether this developmental remodelling is also important for the construction of the mature olivocerebellar projection map, we examined the hypogranular cerebella of rats treated by means of methylazoxymethanol acetate (MAM) during early postnatal life, in which multiple climbing fibre innervation persists in the adult. In these animals we investigated the distribution of calcitonin gene-related peptide (CGRP)-immunoreactive olivocerebellar axons and arbours during early postnatal development, and the correspondence between climbing fibre strips and zebrin II-defined Purkinje cell bands in the adult. Our results show that: (1) the pattern of CGRP-immunoreactive climbing fibres observed during the first three postnatal weeks is not disrupted after granule cell degeneration; and (2) the alignment between olivocerebellar axon subsets and zebrin II+/- Purkinje cell compartments is normally achieved in adult rats. In contrast, the climbing fibre-Purkinje cell relationship is abnormal, and single arbours innervate restricted dendritic regions of several neighbouring target neurons. These results indicate that the normal distribution of olivocerebellar axon subsets to distinct cerebellar cortical compartments can be established independently from granule cell-mediated remodelling processes. Thus, the postnatal climbing fibre plasticity, which is needed to achieve the normal climbing fibre-Purkinje cell relationship, appears to be confined within the framework of a projection map established during earlier developmental phases.

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