Episodic memory: Neuronal codes for what, where, and when.

Episodic memory is defined as the ability to recall events in a spatiotemporal context. Formation of such memories is critically dependent on the hippocampal formation and its inputs from the entorhinal cortex. To be able to support the formation of episodic memories, entorhinal cortex and hippocampal formation should contain a neuronal code that follows several requirements. First, the code should include information about position of the agent ("where"), sequence of events ("when"), and the content of the experience itself ("what"). Second, the code should arise instantly thereby being able to support memory formation of one-shot experiences. For successful encoding and to avoid interference between memories during recall, variations in location, time, or in content of experience should result in unique ensemble activity. Finally, the code should capture several different resolutions of experience so that the necessary details relevant for future memory-based predictions will be stored. We review how neuronal codes in entorhinal cortex and hippocampus follow these requirements and argue that during formation of episodic memories entorhinal cortex provides hippocampus with instant information about ongoing experience. Such information originates from (a) spatially modulated neurons in medial entorhinal cortex, including grid cells, which provide a stable and universal positional metric of the environment; (b) a continuously varying signal in lateral entorhinal cortex providing a code for the temporal progression of events; and (c) entorhinal neurons coding the content of experiences exemplified by object-coding and odor-selective neurons. During formation of episodic memories, information from these systems are thought to be encoded as unique sequential ensemble activity in hippocampus, thereby encoding associations between the content of an event and its spatial and temporal contexts. Upon exposure to parts of the encoded stimuli, activity in these ensembles can be reinstated, leading to reactivation of the encoded activity pattern and memory recollection.