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Cracking the Synaptic Memory Code

Objective

Despite their role in long-term information storage, synapses are highly dynamic and composed of rather short-lived components. In the adult mouse brain, it takes a couple of days for half dendritic spines to be replaced. Similarly at the molecular level most synaptic proteins have half-lives in the order of a week meaning they constantly need to be replaced by freshly produced ones. Thus, understanding how long-term memory can arise from unstable elements is one of todays neurosciences greatest challenges.
Overturning an old dogma, I discovered using in vivo and in vitro approaches that most synapses produce their own proteins locally at both the pre- and postsynaptic sites. Interestingly, classic plasticity paradigms produce unique patterns of rapid pre- and/or postsynaptic translation. This finding is driving a paradigm shift in our understanding of synaptic function. It is now possible to decode pre- and postsynaptic memory traces formed during learning.
I am now in the unique position to combine omics, cytometry, super-resolution and live-imaging techniques, and behavioral learning tasks to unravel how local production of new proteins contributes to information storage at synapses. Firstly, using live-imaging, I want to understand how and when protein synthesis is recruited in excitatory boutons. Secondly, using next generation sequencing and imaging, I will investigate how mRNA find their way to presynapses. Finally, using a genetically encoded neuronal activation tracker, I will follow the molecular changes and thus uncover the synaptic memory traces in the hippocampus and cortex after learning. Altogether, these experiments will tackle from molecules to neural networks the unresolved question of memory encoding in the brain. With an unprecedented resolution, we will gain critical insights into how memories are stored at synapses. Such a fundamental understanding of brain function is needed to provide new avenues against neurodegenerative diseases.

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Keywords

Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)

Programme(s)

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Topic(s)

Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.

Funding Scheme

Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.

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-2022-STG

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Host institution

STICHTING RADBOUD UNIVERSITEIT
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.

€ 1 500 000,00
Address
HOUTLAAN 4
6525 XZ Nijmegen
Netherlands

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Region
Oost-Nederland Gelderland Arnhem/Nijmegen
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.

€ 1 500 000,00

Beneficiaries (1)

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