Project description
The role of human evolution in synapse development
Synapses – the connections between different neurons – play a central role in brain circuits and in the transmission of information, supporting human cognitive abilities. The distribution, maturation and plasticity of human synapses differ from those encountered in rodents or non-human primates. This has urged scientists of the EU-funded SYNPATH project to investigate the molecular mechanisms implicated in the development and plasticity of human synapses, as well as the regulations specific to human synapses, by focusing on the SRGAP2 gene. Through a multi-disciplinary approach that uses mouse and human models, researchers will offer unprecedented evidence on human brain evolution with clinical ramifications for neurodevelopmental disorders.
Objective
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.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences physical sciences optics microscopy super resolution microscopy
- natural sciences biological sciences biochemistry biomolecules proteins
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
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H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC)
MAIN PROGRAMME
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Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
ERC-STG - Starting Grant
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Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
(opens in new window) ERC-2018-STG
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Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.
75654 PARIS
France
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