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Deciphering the enigma of memory persistence: how the brain stably stores information using dynamic networks and unstable neurons

Description du projet

Percer les secrets de la mémoire dans le cerveau

Le cerveau recèle de nombreux mystères non résolus, dont celui du stockage et de la récupération de la mémoire. Grâce à de nouvelles méthodes d’imagerie optique, d’analyse de données à grande échelle et de manipulation des circuits, le projet DYNAMIC_ENGRAM, financé par l’UE, examinera les mécanismes qui contrôlent la réorganisation de la mémoire, en mettant en lumière les facteurs qui régissent la dynamique des circuits des représentations de la mémoire. Les travaux du projet permettront de découvrir comment la consolidation au niveau des systèmes est réalisée au niveau du code neuronal et comment, malgré une représentation neuronale en constante évolution, une mémoire stable est maintenue à long terme.

Objectif

How does the brain store and retrieve information over time? The accepted notion that these processes rely on the neuronal ensembles that were active during learning is now challenged by findings by our lab and others that reveal that different neurons and networks than those that were active during learning support persistent memory. Most notably, we found that the long-term persistence of spatial memory is correlated with the degree to which neuronal activity is spatially informative, but not with the stability of the coding carried by individual neurons. These discoveries—obtained via novel imaging technologies that enable, for the first time, to track large populations of the same neurons over weeks—expose a fundamental gap in our understanding and highlight the need to reveal how neural codes across brain circuits, including the hippocampus, entorhinal cortex, and prefrontal cortex, change over the lifetime of a memory.
Here we propose to investigate the mechanisms that govern the reorganization of memory using innovative methods we recently developed for optical imaging, large-scale data analysis, and circuit manipulation. Key among them is our ability to simultaneously and longitudinally image in two related brain areas the activity of large neuronal populations in freely behaving mice. Using these new tools, we will elucidate the factors governing the circuit dynamics of memory representations (Aim 1); how such dynamics relate to the behavioral manifestation of memory (Aim 2); how hippocampal-cortical and cortical-cortical interactions change over weeks to support remote memory (Aim 3); and what mechanisms could underlie the transfer of learned information between neurons in a network (Aim 4).
Our approach will allow us to resolve how systems-level consolidation is realized at the neural code level, both within and across brain areas, and how a stable memory is maintained over the long term despite an ever-changing neuronal representation.

Champ scientifique (EuroSciVoc)

Mots‑clés

Programme(s)

Thème(s)

Régime de financement

ERC-COG - Consolidator Grant

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Appel à propositions

(s’ouvre dans une nouvelle fenêtre) ERC-2020-COG

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Institution d’accueil

WEIZMANN INSTITUTE OF SCIENCE
Contribution nette de l'UE
€ 2 000 000,00
Coût total
€ 2 000 000,00

Bénéficiaires (1)