Functional role of the neocortico-rubro-olivo-cerebellar circuit on neocortex-induced cerebellar motor learning

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PROJECT SUMMARY The cerebellum performs information processing for motor control and various cognitive functions in cooperation with the cerebral neocortex. One of the anatomical bases for this coordination is the projection from the neocortex to the cerebellum via the parvocellular red nucleus (RNp) and the inferior olive (IO). Because this circuit contains an olivo-cerebellar projection, which is the pathway for the teaching signal to the cerebellum, it has been hypothesized that the neocortical signal of the neocortico-rubro-olivo-cerebellar circuit drives the cerebellar learning to lead the cerebello-neocortical coordination. However, it remains a long- standing theroretical hypothesis due to the lack of substantive experiments. In order to test the hypothesis for the first time, I will examine (1) whether a neocortical signal evoked by electrical stimulation can be a teaching signal to induce cerebellar motor learning, and (2) whether the learning is mediated by the neocortico-rubro- olivo-cerebellar circuit. This will be accomplished by a new approach using the eyeblink conditioning with neocortical US signal, because the eyeblink conditioning paradigm can detect the cerebellar component as an anticipatory eyeblink conditioned response. Also, we will test the cerebellum dependence by inactivating anterior interpositus nucleus. The results of experiments will reveal the functional role of the neocortico-rubro- olivo-cerebellar circuit in motor learning and will give us insights into its role in cognitive ability, because the circuit originates in a wide range of the neocortex including higher cognitive association areas. To understand a new mechanism for cerebello-neocortical coordination will provide a deeper understanding of the pathophysiology due to its impairments and lead new treatment and rehabilitation methods.