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Marighetto, A.

Publications and source records attributed to Marighetto, A..

2 recordsLinked to original sources

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

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.

animal behavior and cognition↗

Autism Spectrum Disorder is a Risk Factor for PTSD-like Memory Formation

A rising concern in Autism Spectrum Disorder (ASD) is the heightened sensitivity to stress and trauma, the potential consequences of which have been overlooked, particularly upon the severity of the ASD traits. This study investigated the predisposition to, and impact of, Post-Traumatic Stress Disorder (PTSD) in ASD. We first demonstrated a reciprocal relationship between the two disorders and revealed that exposure to a mild stressful event induces PTSD-like memory in four mouse models of ASD. We also establish an unanticipated consequence of stress in this condition, showing that the formation of PTSD-like memory leads to the aggravation of the core traits associated with ASD. Such a susceptibility to developing PTSD-like memory in ASD stemmed from hyperactivation of the prefrontal cortex and altered fine-tuning of parvalbumin interneuron firing. We show that this traumatic memory can be treated by recontextualization, reducing the deleterious effects on the core symptoms of ASD. Overall, this study reveals multi-level neurobiological mechanisms that explain the increased vulnerability to develop PTSD in ASD. It provides a framework for future examination of the impact of PTSD-like memory in autism and offers new directions toward behavioral therapeutic interventions targeting traumatic memory in ASD.

neuroscience↗