Descripción del proyecto
Investigación de la plasticidad sináptica en el síndrome del cromosoma X frágil
Las neuronas modifican continuamente sus conexiones con las neuronas cercanas a través de un proceso conocido como plasticidad sináptica, que altera la fuerza y la estructura sináptica. Este proceso está altamente regulado por los receptores N-metil-D-aspartato (NMDA) y permite a las neuronas procesar nueva información. Los científicos del proyecto METAFRAX, financiado con fondos europeos, investigarán la hipótesis de que los receptores NMDA son disfuncionales en el síndrome del cromosoma X frágil (SXF), la causa más común de discapacidad intelectual hereditaria. En un modelo murino de SXF, estudiarán los mecanismos responsables de la alteración de la plasticidad sináptica, lo que contribuirá significativamente a la comprensión de la base molecular de la plasticidad sináptica. El proyecto servirá de base para el futuro descubrimiento de dianas terapéuticas para el SXF y otros trastornos que se presentan con deterioro cognitivo.
Objetivo
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)Coordinador
75794 Paris
Francia