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Authors & Affiliations
Joshua J. White, Daniela Martin-Machado, Iris Van den Heuvel, Anne Huinen, Andrade I. Valea, Erika Goedknegt, Aleksandra Badura, Martijn Schonewille
Abstract
Parasagittal organization is an evolutionarily conserved, fundamental feature of the cerebellar cortex. It is visualized by molecular markers, myelination differences, input and output pathways and susceptibility to degeneration. Different Purkinje cell subpopulations based on molecular marker expression have been shown to exhibit differences in baseline physiological properties, developmental timeline and synaptic plasticity. These subpopulations have also been linked to different cerebellar-dependent learned behaviors. In this study, we demonstrate that these subpopulations exhibit unique physiological responses during the production of the same complex, learned movement. Using a novel “brace conditioning” task, we have successfully trained mice to make a timed, whole-body movement in response to a conditioned stimulus. Mice genetically designed to exhibit cerebellar learning deficits perform more poorly. Using calcium-imaging we demonstrate that during the learning process complex spikes are activated across the cerebellar cortex and their response timing becomes more reliable as the animal learns the task. Finally, using single-unit electrophysiological recordings, we show that Purkinje cell simple spike response is opposite between subpopulations, while still exhibiting complex spikes regardless. These data demonstrate that the specific activity of a Purkinje cell during a learned, complex movement is dependent on the sub-population to which it belongs and can be taught by complex spikes to change their firing in opposite directions. This study shows that subpopulations of Purkinje cells with different intrinsic properties and learning rules work in concert during complex movement.