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Reverse engineering the assembly of the hippocampal scaffold with novel optical and transgenic strategies

Project description

Studying the hippocampus from a developmental perspective

The hippocampus is the part of the brain responsible for learning, emotions and memory formation. Emerging evidence suggests that development plays a key role in hippocampus function. HOPE is an EU-funded initiative that aims to investigate the neural circuits of the hippocampus and whether they are formed during development or are shaped by experience. The project will develop innovative methods that allow the tracing of genetically marked neuronal clones from birth into adulthood. In this way, HOPE will shed light on the emergence and plasticity of neural circuits in both physiological and pathological contexts.

Objective

We aim at shedding a unique light on hippocampal function at circuit level through the design of a novel method to trace the construction of brain circuits in health and disease based on hybrid multiphoton in vivo longitudinal color imaging of the dynamics and structure of genetically-tagged neuronal clones from birth into adulthood. This is made possible by the exceptional interdisciplinary collaboration of three labs with expertise in advanced optical microscopy, genetic engineering and systems developmental neuroscience. Our novel methodology, applied here to the hippocampus, will pioneer a new way to track the emergence and plasticity of heterogeneous neuronal circuits as these progressively give rise to function in physiological and pathological contexts, thus bridging the gap between early development and adult circuit physio-pathology. This will enable us to revisit adult hippocampal function from a developmental perspective. The hippocampus is classically described as providing a cognitive map of space, involved in navigation, learning, and episodic memory. However, a more computational and less representational vision of its role presently emerges in which its circuits are best described as producing sequences of neuronal activation arising from the interaction between external contextual inputs and internally-generated preconfigured dynamics. Converging work including ours leads us to hypothesize that internally preconfigured assemblies, shaped by their developmental journey, are the basic modules of hippocampal function. In this context, we will use our new approach to address three interrelated questions: 1) Are assemblies shaped by specific circuits in the adult hippocampus (objective A)? 2) Are they prewired or shaped by experience (objective B)? 3) What is their patho-physiological significance (objective C)? Addressing these major issues raises a timely challenge in both optics and genetic engineering at the core of this synergistic proposal.

Fields of science (EuroSciVoc)

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Programme(s)

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Topic(s)

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Funding Scheme

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ERC-SyG - Synergy grant

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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-2020-SyG

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Host institution

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS
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.

€ 5 944 088,05
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.

€ 6 017 055,66

Beneficiaries (4)

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