Retrieval uncertainty drives rapid consolidation of confabulated memories in retrosplenial cortex
Learning to make associations in the absence of direct reinforcement, based on previous memories of reward or punishment, is an evolutionary trait quintessential for survival. Little is known about if such higher order associations (HOA) can lead to fabrication of new memories for unreal events. We probed if uncertainty during retrieval of old memory representations can trigger such…
Memories can be formed based on previous experiences of reward or punishment, even without direct reinforcement, a trait crucial for survival. However, it remains unclear if higher order associations (HOA) formed under such circumstances could lead to the creation of new memories for events that never occurred. To investigate this, researchers employed chemogenetics, in vivo imaging, and behavioral studies.
Their findings demonstrate that uncertainty during the retrieval of old memory representations can not only transfer conditioning to unfamiliar contexts but also be rapidly consolidated. The study reveals that while the formation of HOA relies on activity in the dorsal-CA1 parvalbumin interneurons within the intact hippocampus, the retrieval process activates the retrosplenial cortex (RSc).
By developing an automated method called LaBCAM to map functional connectivity changes across brain regions, researchers discovered that only uncertain retrieval in remote contexts triggers the activation of fear circuits, unlike regular retrieval. Furthermore, longitudinal imaging of dendritic spines in the RSc region, which plays a role in detecting and resolving context-dependent conflicts, shows a differential organization of spines during HOA acquisition and its rapid consolidation.
Notably, the study found that HOA is implicated in early stages of Alzheimer's disease (APP/PS1) mice models and aged animals, suggesting its potential relevance in neurodegenerative disorders.
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