Memory formation, storage, and retrieval are fundamental processes that define who we are and how we interact with the world. At the cellular level, these processes rely on specialized neurons called engram cells—neuronal populations that physically encode our experiences and allow us to recall them later. Over the past few decades, scientists have made significant progress in identifying these neuronal ensembles and understanding some aspects of memory allocation.
Although sleep is widely known to be essential for memory processing and consolidation, many of its underlying mechanisms and functions are unclear. Traditional views have largely focused on sleep as a backward-looking process that serves to strengthen past experiences, but could it simultaneously help prepare the brain for new learning?
In a recent effort to tackle this question, a research team from Japan, led by Distinguished Professor Kaoru Inokuchi from the University of Toyama, uncovered a dual role for sleep in memory processing. Their paper, which will be published in Nature Communications on April 28, 2025, explores how the brain simultaneously preserves past memories while preparing for future ones during sleep periods. The study was co-authored by Specially Appointed Assistant Professor Khaled Ghandour, also from the University of Toyama; Dr. Tatsuya Haga from the National Institute of Information and Communications Technology; Dr. Noriaki Ohkawa from Dokkyo Medical University; and Professor Tomoki Fukai from OIST.
The researchers employed an advanced imaging system that combines live calcium imaging with engram cell labeling, allowing them to track neuronal activity in mice before, during, and after learning experiences. This approach gave them unprecedented insights into how specific populations of neurons behave across different cognitive states, including during sleep periods before and after learning events.
Their findings revealed that two parallel processes occur during post-learning sleep. First, engram cells that encoded an initial learning experience showed reactivation patterns—confirming the well-established consolidation process. Remarkably, they also identified a separate population of neurons, which they termed 'engram-to-be cells,' that became increasingly synchronized during post-learning sleep. These cells were later shown to encode a new, different learning experience. "Engram-to-be cells exhibited increased coactivity with existing engram cells during sleep, suggesting that this interaction helps shape new memory networks," explains Prof. Inokuchi.
To understand the mechanisms behind this phenomenon, the team developed a neural network model simulating hippocampal activity. The model suggested that synaptic depression and scaling, which are mechanisms that adjust connection strengths between neurons during sleep, are essential for the emergence of engram-to-be cells. When these processes were disabled in the model, the preparation of neurons for future learning was significantly impaired.
The study also revealed interesting dynamics between existing engram cells and engram-to-be cells, showing increased co-activation during post-learning sleep. This hints at some form of information transfer or coordination between neural networks representing past and future memories.
These findings have significant implications for our understanding of learning and memory. They suggest that the quality of sleep between learning sessions may determine not only how well we remember what we've already learned, but also how effectively we can learn new information. This could influence approaches to education, cognitive enhancement, and the treatment of memory disorders.
Additionally, the research opens new avenues for exploring how sleep disturbances might impact not just memory consolidation but also the brain's preparedness for future learning challenges. "We believe that manipulating brain activity during sleep or sleep patterns may uncover methods to enhance memory by unlocking the brain's latent potential," says Prof. Inokuchi.
Overall, this study underscores the critical role of sleep in maintaining cognitive function and overall well-being. "We want people to understand that sleep is not just about rest—it plays a crucial role in how the brain processes information," Prof. Inokuchi concludes, "With that in mind, we hope everyone will begin to value sleep more and use it as a way to improve their overall quality of life."
