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Epigenetic and transcriptional basis of memory engram plasticity

Objective

Neuroplasticity underlies learning and memory formation, which allows for accumulation of knowledge. There is an emerging view that a sparse ensemble of neurons, termed as engram cells, represent memory substrate and explain how memory is formed and retrieved. Extensive studies have been carried out to reveal molecular mechanisms regulating structural and synaptic plasticity of memory engram cells. However, there are still fundamental questions remaining to be solved regarding epigenetic and transcriptional basis of recent and remote memory formation, and heterogeneous identity specification of engram cells.
To address these issues, I will carry out state-of-the-art genomics/epigenomics analysis of engram cells that are permanently labelled during recent and remote fear memory consolidation. Firstly I will reveal epigenetic and transcriptional mechanisms regulating active-silent state shifts of engram cells during systems memory consolidation in the hippocampus and neocortical regions. Next I will address heterogeneity of engram cells and reveal how a subset of engram cells may become functionally relevant during memory consolidation and retrieval. To particularly address the latter issue, on top of existing sequencing technologies, I will also apply a novel “time machine”-like retrospective whole-genome history tracing approach to obtain molecular profiles of a given timepoint in the past, and overcome the critical limitation of current snapshot-type technologies. To validate relevance of my findings, I will also carry out functional analysis including gene knocking-down and optogenetics approaches.
My interdisciplinary research program will shed new light on how environmental cues, including cell-to-cell interaction mediated by neuronal activity and signalling molecules, can be integrated with intrinsic cellular states at the chromatin epigenetic level to regulate neuroplasticity underlying memory engram cell state and/or identity specification.

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Keywords

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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-2021-STG

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Host institution

AARHUS UNIVERSITET
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.

€ 1 499 948,00
Address
NORDRE RINGGADE 1
8000 Aarhus C
Denmark

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Region
Danmark Midtjylland Østjylland
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.

€ 1 499 948,00

Beneficiaries (1)

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