Consolidating past memories and preparing for future ones — Two processes working simultaneously in the brain during sleep

A research group led by Distinguished Professor Kaoru Inokuchi and Specially Appointed Assistant Professor Khaled Ghandour from the Graduate School of Medicine and Pharmaceutical Sciences, the University of Toyama, along with Researcher Tatsuya Haga from the Center for Information and Neural Networks (CiNet) at the National Institute of Information and Communications Technology, and Associate Professor Noriaki Ohkawa from the Research Center for Advanced Medical Science at Dokkyo Medical University has discovered that the brain simultaneously performs two processes during sleep: consolidating past memories and preparing for future memories. Their findings were announced on April 24. They clarified hippocampal CA1 region neuron activity using original technology for comprehensive observation and mathematical simulations. It is possible that intervention in brain activity during sleep will improve its capacity. The group's research was published in the international journal Nature Communications on April 28.

Research has shown that the brain predicts the near future, that past memories influence future imagination, and that memory exists on a temporal continuum. Recent studies have also shown that the brain regions governing past recall and future imagination are the same. Memories acquired from new experiences are encoded and maintained by sets of multiple neurons (memory engram cells) that were active during the experience, and these memories are recalled when these neurons are reactivated.

The research group had previously built a system that can continuously record neural activity in live mice by placing an endoscopic lens in the mouse hippocampus, simultaneously recording brain waves. They had discovered that fragments (subgroups) of memory engram cell populations that were active during an experience are reactivated during sleep, consolidating and organizing memories, and even storing inferential results not directly experienced but potentially beneficial for the future. They had also confirmed the existence of sets of neurons active during sleep that might also be active during subsequent new experiences.

In this study, the group investigated the possibility that the brain prepares engram cells for future memories during sleep. Specifically, they built an experimental system that distinguished the activity of engram cells from other cells among neurons in the CA1 region of the hippocampus (which governs spatial memory) using different fluorescent dyes and recorded their activity during new experiences and sleep.

They found that about half of the engram cell populations that would be active during Experience A were already active and prepared during sleep before the experience. Non-engram cells were active during the experience but showed no activity before or after it. To investigate when the cells that would become engram cells after Experience A (engram reserve cells) are born, the researchers conducted an experiment in which mice were given two novel experiences.

Specifically, after sleeping in their living space, the mice experienced Space A (a circular room) as Experience A, then slept again in their living space before experiencing Space B (a square room) as Experience B.

The results showed that the engram cell reserve population for Experience B specifically appeared during sleep immediately after Experience A but was not observed during wakefulness.

Analysis of the time sequence of neuronal activity revealed that during sleep after Experience A, the consolidation activity of Experience A engram cells and the activity of Experience B engram reserve cells occurred simultaneously. This suggested that sleep-specific mechanisms might be involved in the emergence of engram reserve cells.

To clarify this mechanism, the researchers created a neural circuit model that mimicked information transmission in hippocampal CA3-CA1 synapses and learning rules during sleep and conducted simulations using mathematical models. Hippocampal CA1 neurons form many synapses with CA3 neurons and receive information from CA3.

The results revealed that engram reserve cell populations emerge through sleep-specific synaptic regulation rules.

While sleep was thought to be for rest, the brain is actually actively working during sleep, with two processes occurring in parallel: "preserving past memories" and "preparing for near-future memories."

Journal Information
Publication: Nature Communications
Title: Parallel processing of past and future memories through reactivation and synaptic plasticity mechanisms during sleep
DOI: 10.1038/s41467-025-58860-w