CORDIS
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CORDIS

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Regulation of synaptic development and plasticity by molecular pathways linked to human evolution

Project information

Grant agreement ID: 803704

Status

Ongoing project

  • Start date

    1 June 2019

  • End date

    31 May 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 500 000

  • EU contribution

    € 1 500 000

Hosted by:

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

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.

Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

Address

Rue De Tolbiac 101
75654 Paris

France

Activity type

Research Organisations

EU Contribution

€ 1 500 000

Beneficiaries (1)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

EU Contribution

€ 1 500 000

Project information

Grant agreement ID: 803704

Status

Ongoing project

  • Start date

    1 June 2019

  • End date

    31 May 2024

Funded under:

H2020-EU.1.1.

  • Overall budget:

    € 1 500 000

  • EU contribution

    € 1 500 000

Hosted by:

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France