To deliberate, remember; to anticipate, forget: Cognitive deliberation profiles underpinning active forgetting-dependent everyday-like memory performance in young and aged mice

Christopher Stevens, Shaam Al Abed, Azza Sellami, Eva Ducourneau, Cathy Lacroix, Mathilde Bouchet, Faustine Roudier, Giovanni Marsicano, Aline Marighetto
. 2023-04-30; :
DOI: 10.1101/2023.04.29.538679

Recalling a specific past episode that will enable us to decide which action is suited to a given present situation is a core element of everyday life. A wealth of research has demonstrated that such selective remembering is dependent upon a capacity to inhibit or provisionally ‘forget’ related yet inappropriate memory episodes which could orient behavior in unwilled directions. Everyday-like memory (EdM) refers to this type of common organizational mnemonic capacity, known to deteriorate significantly with age, putatively as a result of decline in the cognitive capacity for selective inhibition or ‘active forgetting’. Moreover, this memory retrieval-concomitant active forgetting comes at the cost of genuine amnesic weakening of the inhibited episodes, a phenomenon referred to as retrieval-induced forgetting (RIF). In the present study, we introduce a novel characterization of our previously validated mouse model of EdM in terms of the existing active forgetting and RIF literature. We also introduce novel behavioral analyses of the deliberation processes elicited by EdM challenge and use detailed multi-factorial explorations to reveal how these processes are impacted by age, temporal retention demand, difficulty of EdM challenge, and anticipation of trial outcome. Our observations indicate that deliberation requires remembering while accurate anticipation—in which a critical age-related deficit is also observed—requires active forgetting. Our results represent a significant advance towards unifying our understanding of the neurocognitive processes underpinning everyday-like memory, RIF, mnemonic deliberation, anticipatory function, and how they all are impacted by the physiological ageing process. In parallel, we present preliminary results using a transgenic mouse model which point to a fundamental role for the endocannabinoid system (eCS) in active forgetting and EdM, thereby demonstrating that deeper investigation of previously characterized age-related decline of the eCS should be a pre-clinical priority with a view to developing treatments for age-related decline of EdM function.

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