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Decoding the memory engram: bridging neural dynamic and gene expression markers of episodic learning

Objective

How does a memory trace form in the brain? Episodic memories, our autobiographical recollection of past events, are known to depend on the hippocampal circuit. A rich field of research has developed to study the emergence and properties of memory engrams in the hippocampus. Engrams are operationally defined as groups of neurons that are activated during a salient episode, and whose subsequent reactivation can trigger memory recall. But these neural populations are often identified through indirect measures of neural dynamics, using expression of immediate early genes such as Fos to tag and manipulate recently active neurons. By contrast, direct neural recordings in the hippocampus have revealed a repertoire of spatial and navigation-related signals during repetitive exploration and movement. This is typified by place cells, neurons that activate only when an animal occupies specific areas of physical space. Research on place cells and engrams has progressed largely in parallel, and their connections remains highly contested. How do place cells and engram cells build a memory trace? We will address this outstanding question through experiments that combine in vivo identification of engram populations with large scale neural recordings, optogenetic and chemogenetic circuit manipulations, and mouse virtual reality (VR) paradigms. We will first study a novel VR paradigm where mice exhibit fast, episodic learning, and characterize how hippocampal place codes are reshaped by plasticity during few-shot behavioral learning. We will then investigate the links between Fos expression dynamics, place coding, and neural plasticity during episodic learning and recall. Finally, we will test the causal influence of Fos engrams on local hippocampal network dynamics and memory-guided behavior. Our aim is to understand the role of engram populations in neural circuit dynamics, which will provide fundamental insights into the cellular and dynamical substrates of memory.

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Programme(s)

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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-2026-STG

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Host institution

ECOLE POLYTECHNIQUE FEDERALE DE LAUSANNE
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.

€ 1 499 968,00
Address
BATIMENT CE 3316 STATION 1
1015 Lausanne
Switzerland

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Region
Schweiz/Suisse/Svizzera Région lémanique Vaud
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.

€ 1 499 968,00

Beneficiaries (1)