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Changing the tempo of neuronal development to modulate neural circuit function and plasticity

Project description

The role of metabolism in brain development and plasticity

The timing of cell differentiation during development is crucial for the proper formation and function of tissues and organs. Precise regulation of differentiation ensures that cells develop specific identities and roles at the right time and place within the organism. Funded by the Marie Skłodowska-Curie Actions programme, the TEMPOPLAST project focuses on the prolonged development of human cortical neurons that is associated with greater plasticity and complex cognitive processes. Using innovative technologies, researchers will investigate the role of metabolism in neuronal maturation speed, providing fundamental knowledge on human brain development, neurodevelopmental diseases and the ageing brain.

Objective

The timing of neuronal development is highly variable depending on the cell type or species. In particular human cortical neurons display a considerably protracted tempo of development, at the basis of human brain neoteny. The mechanisms underlying neuronal neoteny start to be unravelled, but their significance for brain function and plasticity remain poorly known, despite their implications for brain diseases and repair.
This project will combine innovative technologies developed by the applicant and the host lab, including brain transplantation, molecular manipulation of developmental tempo, and neural connectivity.
Taking advantage of recent findings of the host lab that link metabolism to neuronal maturation speed, we will manipulate mitochondrial function to accelerate the maturation of human neurons in a xenotransplanted mouse model, and conversely, to decelerate murine neurons within the mouse visual cortex. We will thus examine how increasing or decreasing neuronal maturation rates influence functional development, synaptic functions, and experience-dependent plasticity, across time and species. Using advanced techniques including electrophysiology, in vivo calcium imaging, and monocular deprivation neural plasticity paradigms, we will explore the impact of neuronal developmental tempo on cortical circuit function and plasticity. Finally and most excitingly we will use the same paradigms to investigate whether transplanted juvenile neurons can induce plasticity in the neuronal networks of the adult host brain. Additionally, chemogenetic and transsynaptic tracing approaches will dissect potential mechanisms underlying the observed effects. Using MERFISH spatial transcriptomics, we aim to unveil molecular programs driving plasticity induction. This project holds significant potential to reshape our understanding brain development and plasticity, and its implications for neurodevelopmental diseases and therapeutic interventions in the ageing brain.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2023-PF-01

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Coordinator

VIB VZW
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.

€ 175 920,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
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Total cost

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