Dopamine controls whether new declarative information updates reactivated memories through reconsolidation

Abstract

Consolidation and reconsolidation are independent memory processes. Consolidation stabilizes new memories, whereas reconsolidation restabilizes memories destabilized when reactivated during recall. However, the biological role of the destabilization/reconsolidation cycle is still unknown. It has been hypothesized that reconsolidation links new information with reactivated memories, but some reports suggest that new and old memories are associated through consolidation mechanisms instead. Object-recognition memory (ORM) serves to judge the familiarity of items and is essential for remembering previous events. We took advantage of the fact that ORM consolidation, destabilization, and reconsolidation can be pharmacologically dissociated to demonstrate that, depending on the activation state of hippocampal dopamine D1/D5 receptors, the memory of a novel object presented during recall of the memory of a familiar one can be formed via reconsolidation or consolidation, but only reconsolidation can link them. We also found that recognition memories formed through reconsolidation can be destabilized even if indirectly reactivated. Our results indicate that dopamine couples novelty detection with memory destabilization to determine whether a new recognition trace is associated with an active network and suggest that declarative reminders should be used with caution during reconsolidation-based psychotherapeutic interventions.

Optogenetic inactivation of the medial septum impairs long-term object recognition memory formation

“…For example, pre-training intra-hippocampal muscimol administration affects ORM only when the training-test interval is longer than 10 min [ 23 ], suggesting that the hippocampus is not required for short-term ORM recall, that other brain regions take over the role of the hippocampus in short-term ORM processing when it remains disabled for a long time, or that short-term and long-term ORM involve independent mechanisms, as it has been reported for other memory types [ 24 ]. In this regard, our data indicate that the hippocampus is key for long-term ORM formation and substantiate further the idea that the two long-term object memories acquired during training in the novel object recognition task are independent [ 13 ]. Furthermore, the fact that the animals were amnesic only for the object they were exploring when the MS was inactivated strongly indicates that theta is not just a byproduct of learning-induced neural plasticity but is functionally linked to the calculations that occur in the hippocampus during long-term ORM formation.…”

“…To do that, we implanted electrode arrays in the dorsal CA1 region of adult male Wistar rats (3-months-old, 300–350 g) and trained them in the novel object-recognition paradigm, a long-term ORM-inducing task based on the rodents’ natural predilection for novelty that involves exposure to two different but behaviorally equivalent novel objects A and B in a familiar open field arena for 5-min (Fig. 1 a) [ 13 ]. A digital video camera fixed above the arena was utilized for tracking, recording, and analyzing the animals’ position and behavior with the ObjectScan system software (for details see Additional file 1 ).…”

Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease

“…Consistent with previous reports ( Bruce-Keller et al, 2011 ; Chen et al, 2012 ), we confirmed the deterioration of cognitive function with the increase of the age of APP/PS1 mice, which included working memory, short-term spatial memory, long-term recognition memory, and spatial learning and memory. These cognitive tasks mainly reflect the ability of hippocampus-dependent learning and memory ( Zheng et al, 2009 ; Gonzalez et al, 2021 ), and the results hinted at an abnormality of hippocampal function in APP/PS mice at 8 months of age. To exclude the effect of locomotor activity in cognitive tests, we performed OFTs and found that APP/PS1 mice showed decreased locomotor activity in the novel environment at 6 months, but not at 8 months of age.…”

Dopamine D1/D5 Receptors in the Retrosplenial Cortex Are Necessary to Consolidate Object Recognition Memory

“…In addition, blocking dopamine reuptake in the insular cortex of an Alzheimer's disease mice model reversed the STM and LTM object amnesia in those mice (Guzmán-Ramos et al, 2012 ). Moreover, hippocampal dopaminergic tone is essential for object memory persistence (Neves et al, 2020 ; Vargas et al, 2020 ; Lima et al, 2022 ) and reconsolidation (Rossato et al, 2015 ; Gonzalez et al, 2021 ).…”