Plasticity in eye movement control

The cerebellum plays an important role in the recalibration and adaptive adjustment of movements, as well as learning new motor skills and motor related associations. In this thesis, we investigated the mechanisms underlying cerebellar motor learning. To obtain a better understanding, in how the cerebellum processes and stores information, we used specific perturbations that affected the information processing of the cerebellum. Signal transduction pathways were affected that were considered important for cerebellar motor learning by using genetic tools (transgenic mice) and the application of antibodies. Alterations in cerebellar motor learning were studied by monitoring the oculomotor system of these transgenic and treated mice

Oculomotor plasticity during vestibular compensation does not depend on cerebellar LTD

Vestibular paradigms are widely used for investigating mechanisms underlying cerebellar motor learning. These include adaptation of the vestibuloocular reflex (VOR) after visual-vestibular mismatch training and vestibular compensation after unilateral damage to the vestibular apparatus. To date, various studies have shown that VOR adaptation may be supported by long-term depression (LTD) at the parallel fiber to Purkinje cell synapse. Yet it is unknown to what extent vestibular compensation may depend on this cellular process. Here we investigated adaptive gain changes in the VOR and optokinetic reflex during vestibular compensation in transgenic mice in which LTD is specifically blocked in Purkinje cells via expression of a peptide inhibitor of protein kinase C (L7-PKCi mutants). The results demonstrate that neither the strength nor the time course of vestibular compensation are affected by the absence of LTD. In contrast, analysis of vestibular compensation in spontaneous mutants that lack a functional olivocerebellar circuit (lurchers) shows that this form of motor learning is severely impaired. We conclude that oculomotor plasticity during vestibular compensation depends critically on intact cerebellar circuitry but not on the occurrence of cerebellar LTD. Copyrigh