The cerebellum plays a critical role in motor function, but also in cognitive, and social behavioral development. It is proposed that the influence of the cerebellum in high-order processing is via modulatory effects on the cerebral cortex. Importantly, mounting evidences from clinical studies indicate that early cerebellar damage lead to wide range of changes in the structure and function of the developing cerebral cortex. This pathophysiological phenomenon is referred as “developmental diaschisis” and it suggests that the development of cerebral cortical areas is optimized by the guidance of cerebellar input. Thus, abnormalities in the developmental influence between these two brain regions might underlie the emergence of several neurodevelopmental disorders, such as autism spectrum disorders. Yet, the mechanisms by which the cerebellum is influencing the development and maturation of distant cortical circuits remain unknown.
Here, we will adopt a multidisciplinary and innovative approach to define the mechanisms by which the cerebellum influences the development of cortical areas. We hypothesize that these mechanisms are orchestrated by the thalamus, a key intermediate region connecting the cerebellum and the cortex. Therefore, a cerebellar malfunctioning might lead to alterations of cortical areas via thalamic reorganizations. Manipulating cerebellar early normal development and function offers us the possibility to shed light onto this issue. Thus, we will embryonically disturb the cerebello-thalamo-cortical output by anatomical, genetic and functional methods to determine the alterations in the development, organization, function and plasticity of the thalamocortical and cortical networks. The successful execution of this high-risk, high-impact research will provide insights on how the atypical cerebellar structure or function is involved in neurodevelopmental disorders.
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