It has long been hypothesized that a primary function of the hippocampus is to discover and exploit temporal relationships between events. Previously, it has been reported that sequences of "time cells" in the hippocampus extend for tens of seconds. Other studies have shown that neuronal firing in the hippocampus fluctuates over hours and days. Both of these mechanisms could enable temporal encoding of events over very different timescales. However, thus far, these two classes of phenomena have never been observed simultaneously, which is necessary to ascribe broad-range temporal coding to the hippocampus. Using in vivo calcium imaging in unrestrained mice, we observed sequences of hippocampal neurons that bridged a 10 s delay. Similar sequences were observed over multiple days, but the set of neurons participating in those sequences changed gradually. Thus, the same population of neurons that encodes temporal information over seconds can also be used to distinguish periods of time over much longer timescales. These results unify two previously separate paradigms of temporal processing in the hippocampus that support episodic memory.

Summary To provide a substrate for remembering where in space events have occurred, place cells must reliably encode the same positions across long time scales. However, in many cases place cells exhibit instability by randomly reorganizing their place fields between experiences, challenging this premise. Recent evidence suggests that, in some cases, instability could also arise from coherent rotations of place fields, as well as from random reorganization. To investigate this possibility, we performed in vivo calcium imaging in dorsal hippocampal region CA1 of freely moving mice while they explored two arenas with different geometry and visual cues across eight days. The two arenas were rotated randomly between sessions, and then connected, allowing us to probe how cue rotations, the integration of new information about the environment, and the passage of time concurrently influenced the spatial coherence of place fields. We found that spatially coherent rotations of place field maps in the same arena predominated, persisting up to six days later, and that they frequently rotated in a manner that did not match that of the arena rotation. Furthermore, place field maps were flexible, as mice frequently employed a similar, coherent configuration of place fields to represent each arena despite their differing geometry and eventual connection. These results highlight the ability of the hippocampus to retain consistent relationships between cells across long time scales and suggest that, in many cases, apparent instability might result from a coherent rotation of place fields.

While memories are often thought of as flashbacks to a previous experience, they do not simply conserve veridical representations of the past but must continually integrate new information to ensure survival in dynamic environments. Therefore, ‘drift’ in neural firing patterns, typically construed as disruptive ‘instability’ or an undesirable consequence of noise, may actually be useful for updating memories. In our view, continual modifications in memory representations reconcile classical theories of stable memory traces with neural drift. Here we review how memory representations are updated through dynamic recruitment of neuronal ensembles on the basis of excitability and functional connectivity at the time of learning. Overall, we emphasize the importance of considering memories not as static entities, but instead as flexible network states that reactivate and evolve across time and experience.

Highlights d Retrosplenial (RSC) neural populations develop a spatial representation with learning d Late in learning, RSC activity can be used to predict future navigation decisions d After learning, the RSC simulates the correct future reward location d Lesions of the RSC selectively impair alternation performance after learning

Trajectory-dependent splitter neurons in the hippocampus encode information about a rodent’s prior trajectory during performance of a continuous alternation task. As such, they provide valuable information for supporting memory-guided behavior. Here, we employed single-photon calcium imaging in freely moving mice to investigate the emergence and fate of trajectory-dependent activity through learning and mastery of a continuous spatial alternation task. In agreement with others, the quality of trajectory-dependent information in hippocampal neurons correlated with task performance. We thus hypothesized that, due to their utility, splitter neurons would exhibit heightened stability. We find that splitter neurons were more likely to remain active and retained more consistent spatial information across multiple days than other neurons. Furthermore, we find that both splitter neurons and place cells emerged rapidly and maintained stable trajectory-dependent/spatial activity thereafter. Our results suggest that neurons with useful functional coding exhibit heightened stability to support memory guided behavior.