Description du projet
Le rôle du cervelet dans le développement du cortex cérébral
Le cervelet joue un rôle clé dans le contrôle moteur et la cognition. De nouvelles preuves laissent penser que le dysfonctionnement cérébelleux précoce influence ces fonctions en modulant le développement du cortex cérébral. Les chercheurs du projet CERCODE, financé par l’UE, travailleront sur l’hypothèse selon laquelle ce mécanisme est orchestré par le thalamus qui relie le cervelet et le cortex. À cette fin, ils perturberont la connexion cérébello-thalamo-corticale au début du développement et étudieront l’impact sur l’organisation, la fonction et la plasticité des réseaux respectifs. Les résultats permettront de mieux comprendre les mécanismes sous-jacents à l’origine cérébelleuse de plusieurs troubles neurodéveloppementaux, tels que les troubles du spectre autistique.
Objectif
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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Programme(s)
Thème(s)
Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
28006 Madrid
Espagne