Influence of erg potassium channels on rhythmic activity of cerebellar Purkinje cells and motor control of movements

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The aim of the previously approved grant (Schw 292/16-1) is to test the hypothesis, whether the activity of erg K channels in cerebellar Purkinje cells is directly involved in the motor control of balance and of the coordination of body movements. To achieve this goal we want to knock-down erg K channels in Purkinje cells of adult mice by viral transduction of siRNA. We want to investigate at the cellular level whether loss of erg K channels in Purkinje cells influences neuronal activity, like burst activity, and at the level of behavior we want to test the influence of erg K channel loss on motor behavior. The present grant was approved in January 2012. Since then we have performed successfully experiments which showed that in Purkinje cells erg1a channels are presumably mediating the native erg K channels. This result was obtained by quantitative RT-PCR and by performing electrophysiological experiments in which we used erg subunit sensitive toxins. This part of the project has been successfully published in October 2013 in The Journal of Neuroscience. In addition, we have tested two siRNA constructs which effectively inhibit erg1a expression in HEK cells expressing erg1a K channels by about 85%, we have constructed the main part of the viral vector and have established organotypic slices of the cerebellum as a test preparation. We need one additional year to complete the construction and testing of the viral vector, to perform the stereotaxic application of the viral solution to the cerebellum and to perform the investigation of the motor behavior of mice lacking the erg1 K channels in Purkinje cells.