Correlation between multiple climbing fibre regression and parallel fibre response development in the postnatal mouse cerebellum.

ABSTRACT

At the neuromuscular junction elimination of supernumerary synaptic connections during development is owing to a competitive process between single neuronal populations, whereas in the central nervous system the interaction of different types of input could affect the process. In the cerebellum, the regression from multiple- to mono-innervation of the Purkinje cells by climbing fibres is virtually completed during the first two weeks of postnatal development. While it is clear that parallel fibres are important in the control of the regression, there are conflicting results in relation to whether an early phase of regression is independent of parallel fibre effects. We studied the precise timing of climbing fibre synapse development and decline and the relationship with the functional maturation of parallel fibres. Until postnatal day (P) 6 or 7, the synaptic currents generated by different climbing fibres become progressively more uniform in amplitude. However, between P7 and 14, the amplitudes of the currents increasingly diverge until only one fibre remains connected. These data are taken as evidence that, in multiply innervated Purkinje cells, competition between different climbing fibres appears at P7 and continues during the second postnatal week. Morphological and electrophysiological data demonstrate that parallel fibres synapses appear at P7 and their development is significantly correlated with the time course of the climbing fibre regression. These results provide no evidence for climbing fibre regression independent of parallel fibres before P7 and also suggest a dominant role of the parallel fibre input in the later phase.