Selective engram co-reactivation in idling brain inspires implicit learning
概要
A memory is represented by the activity of distinct neurons known as “engram cells”, which are stimulated during a learning experience and consolidated afterwards for future processing. Flexible updating of our past experiences with novel relevant encounters known as “assimilation”, is important for higher-order functions such as implicit learning, creativity, and insight. However, there is a lack of direct causal evidence for the utility of stored neural correlates in the interaction between memories to be formed and pre-existing ones, which this flexibility rationally entails. Moreover, previous work has suggested that the idling states like post-learning sleep could also inspire creative thinking. However, the nature, exclusivity, and necessity of the involved offline processing remain unknown. Here, we show that, parallel to the consolidation of a new experience in the mouse cortex, reactivations of pre-stored engram cells of a subtly related memory spontaneously emerge, leading to their assimilation by extracting their commonality during post-learning sleep. We established a paradigm using mice that links/separates context-dependent memories based on their geometrical similarities. Animals were exposed to one of four environments with different geometric conformations one day before undergoing contextual fear conditioning (CFC) in a square context. Mice showed gradual fear transfer to pre-exposed geometrically-relevant contexts next day, but not after 15 min. CFC memory consolidation rather than assimilation was disrupted upon interference with the post-CFC GABAA receptor-mediated activity of the prelimbic cortex (PL). However, both processes were impaired after similar perturbations in the Anterior Cingulate Cortex (ACC). In vivo calcium imaging revealed that neurons in the ACC representing relevant, rather than distinct, memories were significantly co-reactivated during post-CFC sleep, but not throughout CFC or post-CFC awake periods. Disrupting the ACC co-reactivations during post-CFC sleep by engram-specific optogenetic inhibition of the related memory prevented assimilation while preserving CFC memory consolidation. These results suggest that assimilating pertinent memories during sleep by co-reactivation of their respective engram cells in the ACC represents the neural underpinnings of sleep-triggered implicit learning and extraction of commonalities between life events to update our knowledge. Finally, distinct roles played by the GABAA-mediated modulation of post-encoding activity of ACC and PL indicates the division of labour among cortical circuits, thereby permitting the separation of new experience processing and its assimilation to prior knowledge.