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Synaptic engrams in hippocampal CA3 memory circuits

Project description

Insight into memory engrams in the hippocampus

Learning and memory are driven by the hippocampus, a central brain region that facilitates the formation, storage and retrieval of experiences. Specialised cells have been identified associated with engrams, physical representations of memories in the brain. However, the precise synaptic changes that encode memories remain unclear. The ERC-funded CA3-SYNGRAM project aims to study how engrams form in the CA3 network of the hippocampus, a highly interconnected circuit essential for memory processing. Researchers will follow an interdisciplinary approach to uncover the physical and chemical synaptic changes underlying memory storage and recall. Project results will improve our understanding of memory mechanisms and lead to new treatments for disorders linked to impaired memory formation.

Objective

A fundamental question in neuroscience is how information in brain circuits is stored and retrieved. However, the physical and chemical changes underlying the formation of memories, or “engrams”, are largely elusive. Although recent work identified engram cells, the nanoscopic changes at synapses during engram formation remain unclear. New experimental techniques allow us to probe the subcellular and synaptic components of the engram: functional analysis by multicellular electrophysiology, structural analysis by superresolution light and electron microscopy, and optical recording and stimulation techniques in vivo. Here, we propose to combine these techniques to reveal engrams in the hippocampal CA3 network. This circuit is ideally suited to identify engrams, as it plays a critical role in learning and memory, forms the largest recurrent network throughout the brain, and receives powerful input from hippocampal granule cells, previously defined as engram cells. The project has two main goals. First, we want to identify the physical and chemical changes in the CA3 network during engram formation, especially changes in synaptic transmission and network connectivity. Thus, we will be able to rigorously test cellular, synaptic, and connectomic hypotheses of the engram. Second, we want to probe the rules of synaptic engram storage (“engraphy“), the mechanisms of engram retrieval (“ecphory“), and the behavioral content of the engrams. Hence, we will be able to enrich the classical engram concept with quantitative data on how synaptic engrams are efficiently stored and reliably retrieved. Taken together, the expected results will lead to a substantial increase in our understanding of engrams, advancing it from the cellular to the synaptic level. The proposed experiments will answer a fundamental question in neuroscience and open new avenues for treatment of brain diseases in humans, in which engram formation or retrieval are impaired.

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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-2024-ADG

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Host institution

INSTITUTE OF SCIENCE AND TECHNOLOGY AUSTRIA
Net EU contribution

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€ 2 500 000,00
Address
Am Campus 1
3400 Klosterneuburg
Austria

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Region
Ostösterreich Niederösterreich Wiener Umland/Nordteil
Activity type
Higher or Secondary Education Establishments
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Total cost

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