Studies on activity-dependent maturation of synaptic function during postnatal cerebellar development

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This research aimed at elucidating the mechanisms underlying strengthening of necessary synaptic connections and elimination of redundant ones during postnatal development of the brain. For this purpose, we used climbing fiber to Purkinje cell synapses in the cerebellum as a model system. We have disclosed that postnatal development of climbing fiber to Purkinje cell synapse consists of four distinct phases : (1)functional differentiation, (2)dendritic translocation of a single climbing fiber, (3)early phase of synapse elimination, (4)late phase of synapse elimination. We have elucidated part of the molecular mechanisms underlying each of the four phases. Moreover, we have established an organotipic coculture preparation of cerebellar slices with medulla explants containing the inferior olive. In this preparation, formation and elimination of climbing fiber synapses occur in a manner similar to those seen in vivo. This preparation can be used for screening candidate molecules that may be involved in the development of climbing synapses. Through the five years' research, we have achieved most of the original purposes.