Multiple innervation of cerebellar Purkinje cells by climbing fibres in staggerer mutant mouse

Development of the peripheral nervous system involves an initial overgrowth of synaptic contacts, followed later by the regression of the redundant connections1–4. Similarly, in the central nervous system, the adult-type one-to-one relationship between climbing fibres (CFs) and cerebellar Purkinje cells (PCs) is preceded at early developmental stages by a multiple innervation of PCs by CFs5. The regression of the supernumerary contacts fails to occur when PCs develop in a cellular environment devoid of granule cells6–9, suggesting that it may depend on the formation of synapses between parallel fibres and PCs. However, one cannot preclude the possibility that granule cells intervene in the regressive process by a nonsynaptic action, for instance by emitting a chemical signal at the level of their soma, which could act on the CF-PC synapses. In this respect, the recessive staggerer (sg) mutation10, is of special interest because one of its major phenotypical expressions in homozygous sg/sg animals is the selective and almost complete absence of synapse formation between parallel fibres and Purkinje cells, in spite of the presence of an initially important number of granule cells and of parallel fibres during the synaptogenesis period, that is, until about the end of the 3rd post-natal week. Later on, the relay cells progressively die, probably because of the absence of synaptic contacts with PCs11–13. This is in marked contrast with the other agranular animals studied so far (X-ray irradiated rats and weaver mutant mice6,7,9) where granule cells lack from the very beginning6,9,12. As the staggerer mutation does not prevent the formation of functional synapses between CFs and PCs14, it was important to establish whether PCs can reach the adult-type monoinnervation in the mutant. We show here that each PC is contacted by several CFs in the adult homozygous staggerer mouse, thus supporting the first hypothesis.