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Financement de l’UE (1 500 000 €) : Régulation du développement synaptique et de la plasticité par des voies moléculaires liées à l’évolution humaine Hor14/02/2019 Programme de recherche et d'innovation de l'UE « Horizon »
Vue d’ensemble
Texte
Régulation du développement synaptique et de la plasticité par des voies moléculaires liées à l’évolution humaine
The synapse is a nanoscale machine, which transfers, integrates and stores information in brain circuits. Its function relies on multimolecular networks of interactions whose composition and dynamics shape synaptic transmission. A large body of evidence indicates that synapses specialized in humans. Human synapses are more densely distributed along dendrites and their period of maturation is protracted compared to rodent or non-human primate synapses. The rules governing their plasticity also differ from the other mammalian species studied so far. These traits contribute to the formation and function of complex circuits supporting human cognitive abilities. Yet, the underlying molecular mechanisms are not known. Here we will investigate the role of molecular pathways linked to human evolution in the regulation of synaptic development and plasticity. The proposed research takes advantage of my previous work on Slit-Robo Rho GTPAse-activating protein 2 (SRGAP2), one of the few genes specifically duplicated in humans, and the only one implicated at synapses so far. We will use the duplications of SRGAP2 as a thread to uncover i) fundamental mechanisms of synaptic development and plasticity, and ii) regulations specific to human synapses. To achieve our goals, we will employ a multi-disciplinary approach based on in vivo manipulations in intact mouse cortical circuits, mass spectrometry, live-cell single-molecule super-resolution microscopy, electrophysiology, and engineering of cortical neurons derived from human pluripotent stem cells. The combination of mouse and human models will allow us to establish a robust framework to bridge the gap in knowledge between cellular neurobiology and human brain evolution, and better understand synaptic dysfunctions in neurodevelopmental disorders.
| Institut National de la Sante et de la Recherche Medicale | 1 500 000 € |
https://cordis.europa.eu/project/id/803704
Cette annonce se réfère à une date antérieure et ne reflète pas nécessairement l’état actuel. L’état actuel est présenté à la page suivante : Institut National de la Sante et de la Recherche Medicale, Paris.