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Neural Stem Cell Coordination: a Developmental, Evolutionary and Circuit perspective

Objective

The adult mammalian brain exhibits a remarkable capacity of adaptation, which has long been thought to result from synaptic remodeling of neurons born during development. Importantly, the discovery that new neurons can be generated in the adult by neural stem cells (NSCs) revolutionized our understanding of brain plasticity. In the adult mouse brain, NSCs reside in two specialized niches: the dentate gyrus (DG), and the ventricular-subventricular zone (V-SVZ) lining the lateral ventricles. Although anatomically and functionally different, these two neurogenic regions share several cell types, including the glial NSCs and their lineage, and are sensitive to similar environmental stimuli. This raises the exciting possibility that NSCs within and between niches could coordinate their behavior under specific contexts. I recently showed that in the V-SVZ, regionally-distinct NSC pools can selectively and transiently respond to specific physiological states. However, such spatial and functional stem cell diversity in the DG remains to be investigated.
Here, we hypothesize that the two brain niches form a single plasticity-generator system, comprising multiple stem cell subpopulations, some of which may be inter-dependent. We will first investigate whether some NSC pools across both niches share unexpected molecular features and developmental trajectories. To determine whether and how this V-SVZ/DG system evolved to sustain a plasticity-oriented, regionally-restricted, and transient process in mammals, we will perform comparative transcriptomics with a contrasting model of adult neurogenesis in Zebrafish, which is regeneration-oriented, widespread and continuous. Finally, we will test whether the recruitment of specific adult NSCs in the mammalian brain is orchestrated by neuronal circuit activity outside the niche.
Altogether, our work will uncover the molecular, cellular and circuit logic of adult mammalian neurogenesis in light of NSC heterogeneous identities.

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Keywords

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Topic(s)

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-STG

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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.

€ 1 497 575,00
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.

€ 1 497 575,00

Beneficiaries (1)

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