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Explore how cerebellar dysfunction cascades to impact prefrontal cortex function and cognition in neurodegenerative disease through this 24-minute webinar. Delve into spinocerebellar ataxia type 1 (SCA1), an inherited fatal neurodegenerative disorder caused by abnormal CAG repeat expansions in the ATXN1 gene, which leads to motor, cognitive, and mood deficits along with severe Purkinje cell loss in the cerebellum. Examine research findings from two different SCA1 mouse models, including the transgenic ATXN1[82Q] line that expresses polyglutamine ATXN1 exclusively in cerebellar Purkinje cells and demonstrates impaired cognition. Discover how cerebellar pathology impacts prefrontal cortex function in these mouse models and learn about findings from the novel conditional knock-in f-ATXN1146Q model at early disease stages, which shows increased neuronal numbers and excitatory synapse density in the prefrontal cortex. Understand experimental approaches using mouse and viral genetics, cell and molecular biology techniques, behavioral analysis, fiber photometry, transcriptomics, and disease modeling with induced pluripotent stem cells to investigate cellular and molecular pathways underlying neurodegeneration. Gain insights into how cerebellar dysfunction alone can impact prefrontal cortex function, while also exploring the potential compensatory role of cerebellar dysfunction when multiple brain regions are affected in disease. Learn about the complex relationship between cerebellar and prefrontal cortex function in the context of progressive neurodegeneration and cognitive decline.
