Scientific Understanding of Consciousness
Consciousness as an Emergent Property of Thalamocortical Activity

Medial Entorhinal Cortex replays independently of the Hippocampus


Science  13 Jan 2017: Vol. 355, Issue 6321, pp. 184-188

Superficial layers of the medial entorhinal cortex replay independently of the hippocampus

J. O’Neill,

Institute of Science and Technology Austria (IST Austria), Am Campus 1, A–3400 Klosterneuburg, Austria.


The hippocampus is thought to initiate systems-wide mnemonic processes through the reactivation of previously acquired spatial and episodic memory traces, which can recruit the entorhinal cortex as a first stage of memory redistribution to other brain areas. Hippocampal reactivation occurs during sharp wave–ripples, in which synchronous network firing encodes sequences of places. We investigated the coordination of this replay by recording assembly activity simultaneously in the CA1 region of the hippocampus and superficial layers of the medial entorhinal cortex. We found that entorhinal cell assemblies can replay trajectories independently of the hippocampus and sharp wave–ripples. This suggests that the hippocampus is not the sole initiator of spatial and episodic memory trace reactivation. Memory systems involved in these processes may include nonhierarchical, parallel components.

The hippocampus plays a principal role in the encoding, consolidation, and recall of spatial and episodic memories, by forming cell assemblies that code for place and subsequently replaying their activity patterns. This replay, which represents discrete places or entire movement trajectories, can occur both in waking periods, while animals actively engage in a spatial task, and in periods of rest or sleep; each facilitating different stages of memory processing. During periods of immobility or sleep, replay occurs in highly synchronized network activity during sharp wave–ripples (SWRs) and is associated with memory consolidation. However, SWR-related replay during spatial memory tasks can predict the future behavioral choice of the animal and has been linked to memory recall. Because highly synchronized hippocampal SWR activity recruits multiple brain areas, the prevailing view suggests that the hippocampus initiates replay during SWRs, and in doing so, is the primary coordinator for the consolidation of memory traces associated with place.

By contrast, the entorhinal cortex (EC) is thought to primarily assist the hippocampus in replay-associated mnemonic processing. During encoding, cells in the superficial layers of the medial EC (sMEC), particularly grid cells, provide the hippocampus with precise spatial coding through path integration. However, during SWR-associated replay, the EC is considered to act primarily as a relay, facilitating the transfer of replayed hippocampal memory traces to other cortical areas. Yet, the sMEC and hippocampus may be able to act independently; sMEC cells may take part in replay independently of hippocampal SWRs, initiating memory consolidation or recall. This latter scenario is in agreement with the hypothesis that memory trace reactivation can originate from multiple brain regions.

To test whether the sMEC replays waking experience, and to examine its relationship to hippocampal firing, we simultaneously recorded neurons from the CA1 region and sMEC. Four rats were trained to perform a delayed non–match-to-sample spatial task on a continuous T-maze. Before the task, rats foraged in a large arena to test the two-dimensional spatial firing fields of the sMEC cells that we analyzed.

Our data show that sMEC cells, including grid cells, fired in relation to the memory task on the maze. Furthermore, sMEC was involved in the mnemonic trajectory sequence coding, producing bursts of activity during both waking and sleep or rest that contained sequences reflecting task-related trajectories on the maze. Such events tended to occur independently of hippocampal trajectory replay and associated SWRs. Moreover, trajectory replay that occurred in the sMEC was not associated with temporally aligned coherent activity in CA1. This suggests that the sMEC can trigger its own replay events and initiate recall and consolidation processes independent of hippocampal SWRs, whereas deep EC layers are directly influenced by CA1 replay. However, some weak coordination may exist between CA1 and sMEC, and in some instances, replayed trajectories contain locations that were expressed in the other region.

Overall, these findings indicate that the EC can act independently in mnemonic processes rather than having a subservient role to the hippocampus. Therefore, the hippocampus and the EC may be considered as interrelated but parallel systems in initiating reactivation, and they may recruit different brain pathways and may have different roles.

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