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How the Brain Learns to Forget - The Neural Signature of Fear Memory Erasure

Description du projet

Les mécanismes de l’amnésie post-souvenir

La prévention de l’expression de certains souvenirs émotionnels peut s’avérer bénéfique dans le traitement des patients souffrant de dépression, d’anxiété, de stress post-traumatique et de dépendance. Cette prévention est possible si des interventions pharmacologiques ou comportementales sont administrées au moment de la récupération du souvenir. Ce traitement peut empêcher en permanence le souvenir de refaire surface, mais la science ne sait pas s’il a réellement été effacé. Financé par le Conseil européen de la recherche, le projet WipeOutFear mènera des expériences visant à découvrir les mécanismes sous-jacents de l’amnésie post-souvenir et à déterminer s’il est possible de l’inverser. Le projet prévoit également de développer de nouvelles techniques pour bloquer l’expression des souvenirs émotionnels en déterminant des conditions favorables.

Objectif

Can fear memories be erased from the brain? While it sounds like science fiction, recent findings suggest that fear memories can be undone upon their retrieval, through either pharmacological or behavioural interventions. Still, whether such reconsolidation interference techniques genuinely result in permanent erasure of the original fear memory is a topic of considerable controversy.

Purely behavioural work may never settle the debate, as it cannot be excluded that an apparent loss of fear memory reflects a long-lasting failure to retrieve the fear memory rather than its permanent erasure. We argue that a careful look at the brain memory circuits that control the reduced expression of fear after reconsolidation interference, through imaging studies in humans and inactivation studies in rats, does have the potential to resolve the controversy and decide between erasure and retrieval failure as mechanisms underlying reconsolidation interference [WP1].

To open up a memory trace for reconsolidation interference, it is important that retrieval of the memory is accompanied by surprise or prediction error (PE; a discrepancy between the memory and what actually happens), as we demonstrated in a break-through study in Science (Sevenster, Beckers, & Kindt, 2013). Here, we propose that subtle differences in the degree of PE generated during fear memory retrieval may be what demarcates memory erasure from impaired retrieval. To investigate that claim, we will pioneer an objective neural marker of PE in humans [WP2] and use optogenetics to directly trigger dopamine-based PE signals in the rat brain in order to establish the causal role of PE in enabling fear memory erasure. Along the way, we will investigate the generalization of fear to novel cues as both a problem and a potential target for fear memory modification [WP3] and test an innovative method to interfere with reconsolidation that circumvents limitations of current pharmacological and behavioural techniques [WP4].

Régime de financement

ERC-COG - Consolidator Grant

Institution d’accueil

KATHOLIEKE UNIVERSITEIT LEUVEN
Contribution nette de l'UE
€ 2 000 000,00
Adresse
OUDE MARKT 13
3000 Leuven
Belgique

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Région
Vlaams Gewest Prov. Vlaams-Brabant Arr. Leuven
Type d’activité
Higher or Secondary Education Establishments
Liens
Coût total
€ 2 000 000,00

Bénéficiaires (1)