Mechanisms of Forgetting: Boundaries and conditions for reactivation-mediated attenuation of memory expression

Recent findings have revitalized the notion that memory retrieval is a dynamic process through which a consolidated fear memory can return to a malleable state. In this active state, memory can be affected by pharmacological and behavioral interventions that produce an attenuation of later memory expression (i.e., post-reactivation amnesia). These findings have inspired a plethora of studies investigating the mechanisms and consequences of memory malleability, ranging from basic animal work to (pre)clinical studies in humans, and triggered excitement regarding the prospect of generating new treatments to ameliorate anxiety, post-traumatic stress disorder (PTSD) and substance use disorders in humans. Of importance, most of those studies have been conducted using AAA procedures, where a memory is originally created for a stimulus (be it a discrete cue or context) A, and later reactivated and tested using the exact same stimulus. Importantly, given that future states are never completely identical to past states, human and non-human animals must generalize what they learned from a past experience to future situations that bear a sufficient degree of resemblance to that earlier event. The ultimate goal of this dissertation is to achieve a better understanding in rodents of the mechanism and conditions that govern memory vulnerability when fear memory reactivation occurs through exposure to a generalization situation that perceptually differs from the original situation for which the memory was originally established. To this purpose, we first investigated the mechanism underlying memory malleability to pharmacological and behavioral post-reactivation amnestic interventions in an AAA procedure. Next, we tested whether malleability of a contextual fear memory can be initiated when memory is reactivated through exposure to a generalization situation and what constitute the necessary conditions for such memory malleability to occur. We also investigated to what extent the resulting amnesia can be generalized to yet other situations and what mechanisms underlie this type of amnesia.

Jaar van publicatie:2020

Toegankelijkheid:Open