Flexibility is a hallmark of memories that depend on the hippocampus. For navigating animals, flexibility is necessitated by environmental changes such as blocked paths and extinguished food sources. To better understand the neural basis of this flexibility, we recorded hippocampal replays in a spatial memory task where barriers as well as goals were moved between sessions to see whether replays could adapt to new spatial and reward contingencies. Strikingly, replays consistently depicted new goal-directed trajectories around each new barrier configuration and largely avoided barrier violations. Barrier-respecting replays were learned rapidly and did not rely on place cell remapping. These data distinguish sharply between place field responses, which were largely stable and remained tied to sensory cues, and replays, which changed flexibly to reflect the learned contingencies in the environment and suggest sequenced activations such as replay to be an important link between the hippocampus and flexible memory.

Neurons in hippocampal output area CA1 are thought to exhibit redundancy across cortical and hippocampal inputs. Here we show instead that acute silencing of CA3 terminals drastically reduces place field responses for many CA1 neurons, while a smaller number are unaffected or have increased responses. These results imply that CA3 is the predominant driver of CA1 place cells under normal conditions, while also revealing heterogeneity in input dominance across cells.

Diverse functions such as decision-making and memory consolidation may depend upon communication between neurons in hippocampus (HP) and prefrontal cortex (PFC). HP replay is a candidate mechanism to facilitate this communication, however details remain largely unknown due to the technical challenges of recording sufficient numbers of HP neurons for replay while also recording PFC neurons. Here we implanted male rats with 40-tetrode drives, split between HP and PFC, during learning of a Y-maze spatial memory task. Surprisingly, we found that in contrast to their non-selectivity for maze arm during movement, a portion of PFC neurons were highly selective for HP replay of different arms. Moreover, PFC neurons' selectivity to HP non-local arm representation during running tended to match their replay arm selectivity and was predictive of future choice. Thus, PFC activity that is tuned to HP activity is best explained by non-local HP position representations rather than HP representation of actual position, providing a new potential mechanism of HP-PFC coordination during HP replay.SIGNIFICANCE STATEMENTThe hippocampus is implicated in spatial learning while the prefrontal cortex is implicated in decision-making. The question of how the two areas interact has been of great interest. A specific activity type in hippocampus called replay is particularly interesting because it resembles internal exploration of non-local experiences, but is technically challenging to study, requiring recordings from large numbers of hippocampus neurons simultaneously. Here we combined replay recordings from hippocampus with prefrontal recordings, to reveal a surprising degree of selectivity for replay, and a pattern of coordination that supports some conceptions of hippocampocortical interaction and challenges others.

More than 50 years of research have led to the general agreement that the hippocampus contributes to memory, but there has been a major schism among theories of hippocampal function over this time. Some researchers argue that the hippocampus plays a broad role in episodic and declarative memory, whereas others argue for a specific role in the creation of spatial cognitive maps and navigation. Although both views have merit, neither provides a complete account of hippocampal function. Guided by recent reviews that attempt to bridge between these views, here we suggest that reconciliation can be accomplished by exploring hippocampal function from the perspective of Tolman's (1948) original conception of a cognitive map as organizing experience and guiding behavior across all domains of cognition. We emphasize recent studies in animals and humans showing that hippocampal networks support a broad range of domains of cognitive maps, that these networks organize specific experiences within the contextually relevant map, and that network activity patterns reflect behavior guided through cognitive maps. These results are consistent with a framework that bridges theories of hippocampal function by conceptualizing the hippocampus as organizing incoming information within the context of a multidimensional cognitive map of spatial, temporal, and associational context.

Significance statement

Research of hippocampal function is dominated by two major views. The spatial view argues that the hippocampus tracks routes through space, whereas the memory view suggests a broad role in declarative memory. Both views rely on considerable evidence, but neither provides a complete account of hippocampal function. Here we review evidence that, in addition to spatial context, the hippocampus encodes a wide variety of information about temporal and situational context, about the systematic organization of events in abstract space, and about routes through maps of cognition and space. We argue that these findings cross the boundaries of the memory and spatial views and offer new insights into hippocampal function as a system supporting a broad range of cognitive maps.

The hippocampus is implicated in memory formation, and neurons in the hippocampus take part in replay sequences that have been proposed to reflect memory of explored space. By recording from large ensembles of hippocampal neurons as rats explored various tracks, we show that sustained replay appears after a single experience. Further, we found that with repeated experience in a novel environment, replay slows down, taking more time to traverse the same trajectory. This effect was dependent on experience, not passage of time, and was environment specific. By investigating the slow-gamma (25-50 Hz) hover-and-jump dynamics within replays, we show that replay slows by adding more hover locations, increasing the resolution of the behavioral trajectory. We provide evidence that inhibition and cortical engagement both increase as replay slows. Thus, replays can reflect single experiences and evolve with re-exposure, in a manner consistent with the encoding of greater detail into replay memories with experience.

Decades of rodent research have established the role of hippocampal sharp wave ripples (SPW-Rs) in consolidating and guiding experience. More recently, intracranial recordings in humans have suggested their role in episodic and semantic memory. Yet, common standards for recording, detection, and reporting do not exist. Here, we outline the methodological challenges involved in detecting ripple events and offer practical recommendations to improve separation from other high-frequency oscillations. We argue that shared experimental, detection, and reporting standards will provide a solid foundation for future translational discovery.