A Role for the Medial Entorhinal Cortex in Multimodal Information Processing and Episodic Memory

The hippocampus and medial entorhinal cortex (mEC) have been together implicated in the cognitive processes of episodic memory and spatial navigation. Through collective network activity, hippocampal place cells provide a map of the world that could support navigation. In conjunction, remapping in the place cell network provides a mechanism to support episodic memory, allowing for individual episodes to be readily distinguished and reliably recalled. Upstream in mEC, spatial firing patterns are robust, but the ability of mEC cells to remap and provide a signal to support episodic memory has remained largely untested. We recorded mEC cells while altering the features of an explored environment to determine if mEC may play a role in episodic memory processing. Indeed, we observed changes in the firing rates of mEC grid cells and the spatial firing patterns of non-grid spatial cells in response to environment manipulations, indicating that information necessary to distinguish between experiences was contained in mEC network activity. Yet, while distinguishing between events represents a central tenant of episodic memory, an additional requirement is the evaluation of a temporal component. How long ago experiences occur, and in what order, can be just as relevant as what actually happened. Systematic drift in network representations over time represents a candidate mechanism for encoding such temporal information. Drift has been repeatedly observed in the CA1 network, but the origin of such a signal remains unclear. To pursue this question, we recorded CA2 and mEC cells over many hours, evaluating how representations changed, or remained stable, over time. In CA2 we found considerable variation over time, well in excess of that in CA1. Upstream in mEC, a small minority of cells exhibited temporal drift, but overall the representation was reliable, suggesting the primary role of mEC may be to anchor downstream hippocampal representations. Collectively, our work indicates that the conjunctive coding schemes observed in place cells are not unique to the hippocampus, but that upstream the mEC appears to serve a similar role in providing a multimodal representation of an animal’s interactions with the outside world to support both spatial navigation and episodic memory