Reciprocal trophic interactions between climbing fibres and Purkinje cells in the rat cerebellum.

In the adult cerebellum both the climbing fibre arbour and the Purkinje cell are very plastic and each element is able to exert a remarkable action on the other one. The adult phenotype of the Purkinje cell is strictly dependent on the presence of its climbing fibre arbour. When the climbing fibre is missing, the Purkinje cell undergoes a hyperspiny transformation and becomes hyperinnervated by the parallel fibres. However, this change is fully reversible. The climbing fibre-deprived Purkinje cell is able to elicit sprouting of nearby located intact climbing fibres and the new arbour is able to fully restore synaptic connections which appear normal both morphologically and functionally. Multiple climbing fibre innervation of a single Purkinje cell persists in the adult hypogranular cerebellum. The different fibres are distributed to separate dendritic regions, suggesting a local competition between the different arbours for their territory. It is postulated that in the intact rat, an activity dependent mechanism of the parallel fibre favours the predominance of one arbour with the elimination of its competitors. When the Purkinje cell is deleted, the climbing fibre arbour becomes heavily atrophic and reduced in size. The analysis of the pattern of this atrophy indicates that the climbing fibre arbour is made by two compartments: a proximal one, whose survival depends on the integrity of the inferior olive, and a distal one, which represents the true pre-synaptic site, which strictly depends on the target. The climbing fibre terminal arbour is able to extend its territory of innervation not only when adult intact climbing fibres are confronted with nearby denervated Purkinje cells, but also when an embryonic cerebellum is grafted onto the surface of an adult unlesioned cerebellum. In this case, collaterals of intact climbing fibre arbours elongate through the pial surface, enter the graft to innervate the Purkinje cells. This growth is likely under the influence of a tropic signal released by the embryonic Purkinje cells. This suggests that the sprouting observed in the adult rat following a subtotal inferior olive lesion is also triggered by a similar factor. The axonal elongation and the consequent synaptogenesis are likely guided by local cues. In this condition, the distribution of the new collateral reinnervation occurs within its projectional map. In addition, when the inferior cerebellar peduncle is sectioned at birth, the climbing fibres of the non-deafferented hemicerebellum emit collaterals which cross the midline and innervate cerebellar strips which are symmetrically positioned relative to the intact side. In the grafting experiments, both the migrated and non-migrated Purkinje cells show the typical electrophysiological properties of the mature cerebellum. These data show that the disappearance of neuronal elements is not a necessary prerequisite to allow new neurones to become fully morphologically and functionally integrated into an adult brain. The reciprocal trophic influence between the climbing fibres and the Purkinje cells shown in the present series of experiments are likely operative in the adult brain not only in pathological conditions and they could give a basic contribution to the synaptic plasticity underlying learned behaviour.