A consensus statement on detection of hippocampal sharp wave ripples and differentiation from other fast oscillations.

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.

The grid code for ordered experience.

Entorhinal cortical grid cells fire in a periodic pattern that tiles space, which is suggestive of a spatial coordinate system. However, irregularities in the grid pattern as well as responses of grid cells in contexts other than spatial navigation have presented a challenge to existing models of entorhinal function. In this Perspective, we propose that hippocampal input provides a key informative drive to the grid network in both spatial and non-spatial circumstances, particularly around salient events. We build on previous models in which neural activity propagates through the entorhinal-hippocampal network in time. This temporal contiguity in network activity points to temporal order as a necessary characteristic of representations generated by the hippocampal formation. We advocate that interactions in the entorhinal-hippocampal loop build a topological representation that is rooted in the temporal order of experience. In this way, the structure of grid cell firing supports a learned topology rather than a rigid coordinate frame that is bound to measurements of the physical world.

Spatial Responses, Immediate Experience, and Memory in the Monkey Hippocampus.

Debate about the function of the hippocampus often pits theories advocating for spatial mapping against those that argue for a central role in memory. This review addresses whether research in the monkey supports the view that processing spatial information is fundamental to the function of the hippocampus. In support of spatial processing theories, neurons in the monkey hippocampal formation have striking spatial tuning, and an intact hippocampus is necessary to effectively utilize allocentric spatial relationships. However, the hippocampus also supports non-spatial processes, as its neurons acutely respond to distinct task events and hippocampal damage disrupts both expedient task acquisition and the monitoring of ongoing events in non-spatial paradigms. The features that are shared between spatial and non-spatial hippocampal-dependent tasks point toward a common mechanism underlying hippocampal function that is independent of processing spatial information. We suggest that spatial information is only one facet of immediate experience represented by the hippocampus. The current data support the idea that the hippocampus tracks many aspects of ongoing experience and the primary role of the hippocampus may be in linking experienced events into unitary episodes.

Medial Entorhinal Cortex Selectively Supports Temporal Coding by Hippocampal Neurons.

Recent studies have shown that hippocampal "time cells" code for sequential moments in temporally organized experiences. However, it is currently unknown whether these temporal firing patterns critically rely on upstream cortical input. Here we employ an optogenetic approach to explore the effect of large-scale inactivation of the medial entorhinal cortex on temporal, as well as spatial and object, coding by hippocampal CA1 neurons. Medial entorhinal inactivation produced a specific deficit in temporal coding in CA1 and resulted in significant impairment in memory across a temporal delay. In striking contrast, spatial and object coding remained intact. Further, we extended the scope of hippocampal phase precession to include object information relevant to memory and behavior. Overall, our work demonstrates that medial entorhinal activity plays an especially important role for CA1 in temporal coding and memory across time.

Rhythmic coordination of hippocampal neurons during associative memory processing.

Hippocampal oscillations are dynamic, with unique oscillatory frequencies present during different behavioral states. To examine the extent to which these oscillations reflect neuron engagement in distinct local circuit processes that are important for memory, we recorded single cell and local field potential activity from the CA1 region of the hippocampus as rats performed a context-guided odor-reward association task. We found that theta (4-12 Hz), beta (15-35 Hz), low gamma (35-55 Hz), and high gamma (65-90 Hz) frequencies exhibited dynamic amplitude profiles as rats sampled odor cues. Interneurons and principal cells exhibited unique engagement in each of the four rhythmic circuits in a manner that related to successful performance of the task. Moreover, principal cells coherent to each rhythm differentially represented task dimensions. These results demonstrate that distinct processing states arise from the engagement of rhythmically identifiable circuits, which have unique roles in organizing task-relevant processing in the hippocampus.

Transient optogenetic inactivation of the medial entorhinal cortex biases the active population of hippocampal neurons.

The mechanisms that enable the hippocampal network to express the appropriate spatial representation for a particular circumstance are not well understood. Previous studies suggest that the medial entorhinal cortex (MEC) may have a role in reproducibly selecting the hippocampal representation of an environment. To examine how ongoing MEC activity is continually integrated by the hippocampus, we performed transient unilateral optogenetic inactivations of the MEC while simultaneously recording place cell activity in CA1. Inactivation of the MEC caused a partial remapping in the CA1 population without diminishing the degree of spatial tuning across the active cell assembly. These changes remained stable irrespective of intermittent disruption of MEC input, indicating that while MEC input is integrated over long time scales to bias the active population, there are mechanisms for stabilizing the population of active neurons independent of the MEC. We find that MEC inputs to the hippocampus shape its ongoing activity by biasing the participation of the neurons in the active network, thereby influencing how the hippocampus selectively represents information.