Abstract
Reactivated long-term memories can become labile and sensitive to modification. Memories in this destabilized state can be weakened or strengthened, but there is limited research characterizing the mechanisms underlying retrieval-induced qualitative updates (i.e., information integration). We have previously implicated cholinergic transmission in object memory destabilization. Here we present a novel rodent paradigm developed to assess the role of this cholinergic mechanism in qualitative object memory updating. The post-reactivation object memory modification (PROMM) task exposes rats to contextual information following object memory reactivation. Subsequent object exploratory performance suggests that the contextual information is integrated with the original memory in a reactivation- and time-dependent manner. This effect is blocked by interference with M1 muscarinic receptors and several downstream signals in perirhinal cortex. These findings therefore demonstrate a hitherto unacknowledged cognitive function for acetylcholine with important implications for understanding the dynamic nature of long-term memory storage in the normal and aging brain.
Highlights
Reactivated long-term memories can become labile and sensitive to modification
Retrieval enables constructive and time-dependent object memory updating in rats
In order to verify that ubiquitin proteasome system (UPS) activation is important for the object memory updating measured by the post-reactivation object memory modification (PROMM) task, we evaluated the effect of blocking 26 S proteasome activity prior to memory reactivation directly within perirhinal cortex (PRh) using pre-reactivation intra-PRh microinjections of the proteasome inhibitor clasto-lactacystin β-lactone (β-lac)
Summary
Reactivated long-term memories can become labile and sensitive to modification. Memories in this destabilized state can be weakened or strengthened, but there is limited research characterizing the mechanisms underlying retrieval-induced qualitative updates (i.e., information integration). Studies in rodents and humans have demonstrated post-reactivation modification by manipulating the strength of fear memory, providing evidence for memory trace weakening or erasure[4,8], as well as strengthening through targeted additional training[9] These studies do not directly assess the integration of new, relevant information presented during the reconsolidation window to update the content of established long-term memories. Analogous to the study just mentioned, which used objects to study updating of declarative memory in humans, here we present a novel paradigm for use with rodents to investigate the behavioural and neural mechanisms of reconsolidation-based object memory updating In this post-reactivation object memory modification (PROMM) task, new contextual information appears to be incorporated into a previously acquired object memory when presented while the object memory trace is labile following reactivation
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