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Human-specific modifiers of synapses in development, plasticity and disorders

Project description

What makes human synapses unique

The human brain’s extraordinary abilities (thinking, learning, adapting) rely on synapses, the tiny contact points between neurons. While synapses are broadly similar across mammals, studies suggest they are regulated differently in humans, helping to shape the extended brain development and complex behaviours that define our species. In this context, the ERC-funded synMODIFIERS project explores how uniquely human genetic innovations influence synapse formation, maturation, and plasticity. It also studies how this may relate to neurodevelopmental disorders. Using advanced mouse and human models, combined with molecular, electrophysiological, and omics approaches, the project aims to uncover the distinct biology of human synapses. The goal is to better understand how our brains develop.

Objective

The function of the brain relies on an intricate network of neurons connected by synapses that enable us to feel, think, learn, act, communicate and adapt our behavior to the ever-changing world. Although the molecular composition and organization of synapses are overall conserved across mammals, a large body of evidence indicates that synapses are differentially regulated in humans. This specialization of human synapses is at the heart of what makes us human. It contributes to the increase in connectivity that characterizes the human neocortex. It also extends the period of synaptic maturation during which cognitive and social experiences sculpt developing cortical circuits and many neurodevelopmental disorders manifest. In this project, we will test the hypothesis that human-specific genetic innovations enhance the role of the environment in the development of synapses in cortical circuits and impact the pathophysiology of neurodisorders. Building on recent advances in our understanding of the human genome, we will determine how human-specific genetic innovations modify the cell biology of synapses, from synaptic connectivity and maturation to synaptic plasticity and pathological dysfunctions. We will combine cutting-edge mouse and human models compatible with investigation of synapse cell biology in integrated circuits together with a multidisciplinary approach based on in vivo molecular manipulations, electrophysiology, microscopy and omics technologies. This will allow us to gain a comprehensive understanding of fundamental mechanisms and illuminate species differences between mouse and human at the synapse and in neurodisorders, in a way not previously possible and with broad implications for the development of therapeutic strategies.

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.

(opens in new window) ERC-2024-COG

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Host institution

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
Net EU contribution

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.

€ 2 000 000,00
Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 000 000,00

Beneficiaries (1)

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