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How dendritic mRNA and protein distributions shape synaptic plasticity

Project description

Solving the puzzle of synaptic protein numbers regulation

Neurons regulate dendritic protein numbers and redistribute proteins in response to synaptic changes. However, the way the available pool of proteins is redistributed via diffusion or active trafficking and how synaptic protein numbers are modified by increased translation of local mRNAs is a mystery. The EU-funded MolDynForSyn project aims to develop a data-driven theory describing the dendritic mRNA and protein distributions and use it to study the synaptic plasticity dynamics in dendrites and their impact on memory storage. The unique combination of theoretical and experimental data will result in a better understanding of long-term memory mechanisms and many neurological diseases associated with neuronal trafficking pathologies or protein synthesis dysfunction.

Objective

Proteins are the building blocks of life and neurons constantly need proteins to remain functional. This is a formidable challenge because neurons must regulate dendritic protein numbers across hundreds of micrometers, and need to redistribute proteins quickly in response to any synaptic changes. For example, long-term plasticity requires new proteins. Yet, it is still a puzzle how the available pool of proteins is redistributed via diffusion or active trafficking and how synaptic protein numbers are modified by increased translation of local mRNAs. Similarly, it is now an open question how the dysregulation of mRNA transport translates into plasticity impairments, how these modify circuit functions and ultimately lead to cognitive impairments. To answer these questions and connect the molecular dynamics to circuit function, we will develop a data-driven theory describing the dendritic mRNA and protein distributions in space and time and will use it to study the emergent synaptic plasticity dynamics in dendrites and its impact on memory storage. We will use data from leading experimental labs to identify how the unique combination of dendritic mRNAs, dendritic morphology, and synaptic activity gives rise to the synaptic protein dynamics that shapes circuit function. Our theory framework will generate and test hypotheses about how individual components such as mRNA motion, translation or degradation shape the protein exchange between synapses and clarify how they translate into multi-synapse synaptic plasticity rules that give rise to memory formation, memory generalization and separation. The unique combination of theory and experimental data will improve our understanding of long-term memory mechanisms and numerous neurological diseases that are associated with neuronal trafficking pathologies or protein synthesis dysfunction.

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Topic(s)

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ERC-STG - Starting Grant

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Call for proposal

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(opens in new window) ERC-2020-STG

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Host institution

UNIVERSITATSKLINIKUM BONN
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.

€ 1 207 285,16
Address
VENUSBERG-CAMPUS 1
53127 BONN
Germany

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Region
Nordrhein-Westfalen Köln Bonn, Kreisfreie Stadt
Activity type
Higher or Secondary Education Establishments
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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.

€ 1 207 285,16

Beneficiaries (1)

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