Molecular and Circuit Mechanisms for Hippocampal Learning

The hippocampus is crucial for the formation of memories of facts and episodes (Scoville and Milner 1957; Jarrard 1993; Squire et al. 2004; Burgess et al. 2002). In storing the contents of a specific episode, the hippocampus must rapidly form and maintain representations of the temporal and spatial relationship of events and keep these representations distinct, allowing similar episodes to be distinguished, a property termedpattern separation. Furthermore, because specific episodes are rarely replicated in full, the hippocampus must be capable of using partial cues to retrieve previously stored patterns of representations, a phenomenon referred to as pattern completion. Based primarily on the anatomy (Fig. 1) and physiology of the hippocampus and its associated cortical structures, computational neuroscientists have suggested specific hippocampal subregions andcircuits thatmay subserve thesemnemonic requirements. These are the feedforward pathway from the entorhinal cortex (EC) to the dentate gyrus (DG) and on to CA3 for pattern separation, and the recurrent and highly plastic connections in CA3 for pattern completion (Marr 1971;McClelland andGoddard 1996; McNaughton and Nadel 1990; O’Reilly and McClelland 1994).