The role of experience in prioritizing hippocampal replay.

During sleep, recent memories are replayed by the hippocampus, leading to their consolidation, with a higher priority given to salient experiences. To examine the role of replay in the selective strengthening of memories, we recorded large ensembles of hippocampal place cells while male rats ran repeated spatial trajectories on two linear tracks, differing in either their familiarity or number of laps run. We observed that during sleep, the rate of replay events for a given track increased proportionally with the number of spatial trajectories run by the animal. In contrast, the rate of sleep replay events decreased if the animal was more familiar with the track. Furthermore, we find that the cumulative number of awake replay events occurring during behavior, influenced by both the novelty and duration of an experience, predicts which memories are prioritized for sleep replay, providing a more parsimonious neural correlate for the selective strengthening of memories.

Experience-driven rate modulation is reinstated during hippocampal replay.

Replay, the sequential reactivation within a neuronal ensemble, is a central hippocampal mechanism postulated to drive memory processing. While both rate and place representations are used by hippocampal place cells to encode behavioral episodes, replay has been largely defined by only the latter - based on the fidelity of sequential activity across neighboring place fields. Here, we show that dorsal CA1 place cells in rats can modulate their firing rate between replay events of two different contexts. This experience-dependent phenomenon mirrors the same pattern of rate modulation observed during behavior and can be used independently from place information within replay sequences to discriminate between contexts. Our results reveal the existence of two complementary neural representations available for memory processes.

How do our brains store memories? We now know that this is a complex and dynamic process, involving multiple regions of the brain. A brain region, called the hippocampus, plays an important role in memory formation. While we sleep, the hippocampus works to consolidate information, and eventually creates stable, long-term memories that are then stored in other parts of the brain. But how does the hippocampus do this? Neuroscientists believe that it can replay the patterns of brain activity that represent particular memories. By repeatedly doing this while we sleep, the hippocampus can then direct the transfer of this information to the rest of the brain for storage. The behaviour of nerve cells in the brain underpins these patterns of brain activity. When a nerve cell is active, it fires tiny electrical impulses that can be detected experimentally. The brain thus represents information in two ways: which nerve cells are active and when (sequential patterns); and how active the nerve cells are (how fast they fire electrical impulses or firing rate). For example, when an animal moves from one location to another, special place cells in the hippocampus become active in a distinct sequence. Depending on the context, they will also fire faster or slower. We know that the hippocampus can replay sequential patterns of nerve cell activity during memory consolidation, but whether it can also replay the firing rates associated with a particular experience is still unknown. Tirole, Huelin Gorriz et al. set out to determine if the hippocampus could also preserve the information encoded by firing rate during replay. In the experiments, rats explored two different environments that they had not seen before. The activity of the rats' place cells was recorded before and after they explored, and also later while they were sleeping. Analysis of the recordings revealed that during replay, the rats' hippocampi could indeed reproduce both the sequential patterns of activity and the firing rate of the place cells. It also confirmed that each environment was associated with unique firing rates ­ in other words, the firing rates were memory-specific. These results contribute to our understanding of how the hippocampus represents and processes information about our experiences. More broadly, they also shed new light on how the brain lays down memories, by revealing a key part of the mechanism that it uses to consolidate that information.