The Human Dentate Gyrus Plays a Necessary Role in Discriminating New Memories

Abstract

Our day-to-day experiences are often similar to one another, occurring in the same place at the same time of day, with common people and objects, and with a shared purpose. Humans have an episodic memory to represent unique, personal events that are rich in detail [1]. For this to occur, at least two basic neural mechanisms are required: one to orthogonalize or "separate" overlapping input patterns at encoding and another to reinstate or "complete" memories from partial cues at retrieval [2-6]. To what extent do these purported "pattern separation" and "pattern completion" mechanisms rely on distinct subfields of the hippocampus [6]? Computational models [4-6] and lesion and genetic studies in rodents [7-12] largely point to the dentate gyrus as responsible for pattern separation and the CA3 andCA1 subfields for pattern completion (but see [13-16]). In high-resolution fMRI studies of humans, behavioral discrimination and completion tasks designed to approximate pattern separation and pattern completion, respectively, elicit the predicted pattern of activity in the dentate gyrus and CA3/CA1 [17-21]. Likewise, impaired behavioral discrimination has been demonstrated in individuals with hippocampal lesions [22, 23], but the lesions most likely encompass other subfields. Examination of these processes in individuals with selective lesions to hippocampal subfields is needed to infer causation [19]. Here, we report the rare case of BL, a 54-year-old man with bilateral ischemic lesions to the hippocampus [24] primarily affecting the dentate gyrus. Studying BL provides the unique opportunity to directly evaluate theories of hippocampal function that assign the dentate gyrus a specific role in discriminating old from new memories.