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Neural circuit mechanisms of memory destabilization

Project description

Finding the neurons that can rewrite memories

Science fiction filmmakers and novelists love to explore the theme of memory manipulation – from mass memory wiping to memory editing. In reality, it is theoretically possible to rewrite a memory. The all-limiting step in this memory re-evaluation process is its initiation – the retrieval-dependent destabilisation of the memory. Research has shown that memories can be destabilised if reactivated. However, in some conditions, for example when memories are very strong, they seem to be protected from being changed. The question is how a memory can be modified so that it becomes malleable again, even with those boundary conditions in place? The EU-funded DstablizeMemory project will further our understanding of the neural circuits crucial for destabilising memory. It will examine the networks that impose restrictive conditions to gate reconsolidation and will explore the role of targeted protein degradation in the destabilisation of memory.

Objective

Memories can be rendered rewritable through a phenomenon called reconsolidation. The all-limiting step in this memory re-evaluation process is its initiation; the retrieval-dependent destabilization of the memory. However, the understanding of how a stable memory can be switched into a vulnerable but modifiable state is mostly in its infancy. Therefore, I aim to investigate the neural circuit mechanisms underlying retrieval-induced memory destabilization in the tractable fruit fly brain.

A prerequisite to investigate the neural mechanisms involved in destabilizing a memory is to know where the learned information is stored and to have access to the associated network. Olfactory memories in flies are stored in the mushroom body as changes between odor coding principle cells and valence coding output neurons. The cell specific genetic access to the 2500 neurons of each mushroom body allows to manipulate and monitor the activity of all components of the network in behaving animals. Recently I established a paradigm that allows to study the mechanisms underlying memory reconsolidation in this numerically simple brain structure. First results indicate that I have identified specific neurons which are crucial for destabilizing reward memory. Starting from these findings I will study the neural circuit mechanisms involved in memory destabilization.

I aim to generate an understanding of
1) the neural circuits underlying memory destabilization
2) how restrictive conditions gate reconsolidation
3) the role of targeted protein degradation in the destabilization of memory

The work will establish the first mechanistic insight into how memories are destabilized, how a destabilized memory is represented in the brain and how boundary conditions prevent the initiation of memory reconsolidation.

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Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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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

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH FONDATION
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
FABRIKSTRASSE 2
4056 BASEL
Switzerland

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Region
Schweiz/Suisse/Svizzera Nordwestschweiz Basel-Stadt
Activity type
Research Organisations
Links
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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