Description du projet
Étude de la plasticité synaptique dans le syndrome de l’X fragile
Les neurones modifient constamment leurs connexions avec les neurones environnants par le biais d’un processus appelé plasticité synaptique, qui altère la force et la structure des synapses. Ce processus est hautement régulé par les récepteurs NMDA (NMDAR) et permet aux neurones de traiter les nouvelles informations. Les scientifiques du projet METAFRAX, financé par l’UE, étudieront l’hypothèse selon laquelle les NMDAR présentent un dysfonctionnement dans le syndrome de l’X fragile (FXS), la cause la plus courante de déficience intellectuelle héréditaire. Ils étudieront sur un modèle murin de FXS les mécanismes responsables des altérations de la plasticité synaptique, en contribuant ainsi grandement à la compréhension de la base moléculaire de la plasticité synaptique. Le projet servira de base pour la découverte de futures cibles thérapeutiques pour le FXS et d’autres affections caractérisées par une déficience cognitive.
Objectif
Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability (ID), and the leading known genetic cause of autism. This dominant phenotype represents a huge hindrance for clinicians in the treatment of FXS because the underlying neuronal deficits remain unknown. Individual neurons store information as we learn and acquire new information by modifying their connections with nearby neurons, a process called synaptic plasticity. This refers to activity-dependent long-term changes in synaptic strength but also synaptic structure, and is highly regulated by NMDA receptors (NMDAR). It has recently been proposed that NMDARs can signal in an unconventional manner. Our goal is to understand how unconventional NMDRs drive synaptic plasticity, and how this is dysregulated in the mouse model of FXS. For this, we will record electrical activity of the neurons and image synaptic structures during different forms of synaptic plasticity, and characterise metabotropic NMDAR signaling by functional genomic approaches.
In summary, we will use a multi-disciplinary approach to unravel the mechanisms responsible for synaptic plasticity alteration in the mouse model for FXS and further our understanding of the neuronal processes underlying cognitive phenotypes of FXS. The outcomes of these experiments will not only offer hope to patients with FXS but will also further our understanding of the molecular basis of synaptic plasticity. If successful, this could serve as the basis for future molecular targets to promote cognitive recovery from ID, autism spectrum disorders and other diseases.
The project is an excellent opportunity for the researcher to further develop her knowledge and to position her in unique multidisciplinary environment that will foster her career progression towards independence. The researcher’s experience acquired at MIT and during the outgoing phase at McGill will be extremely valuable for the host institution and the European research area.
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MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinateur
75794 Paris
France