The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory

Abstract

Both recognition of familiar objects and pattern separation, a process that orthogonalises overlapping events, are critical for effective memory. Evidence is emerging that human pattern separation requires dentate gyrus. Dentate gyrus is intimately connected to CA3 where, in animals, an autoassociative network enables recall of complete memories to underpin object/event recognition. Despite huge motivation to treat age-related human memory disorders, interaction between human CA3 and dentate subfields is difficult to investigate due to small size and proximity. We tested the hypothesis that human dentate gyrus is critical for pattern separation, whereas, CA3 underpins identical object recognition. Using 3 T MR hippocampal subfield volumetry combined with a behavioural pattern separation task, we demonstrate that dentate gyrus volume predicts accuracy and response time during behavioural pattern separation whereas CA3 predicts performance in object recognition memory. Critically, human dentate gyrus volume decreases with age whereas CA3 volume is age-independent. Further, decreased dentate gyrus volume, and no other subfield volume, mediates adverse effects of aging on memory. Thus, we demonstrate distinct roles for CA3 and dentate gyrus in human memory and uncover the variegated effects of human ageing across hippocampal regions. Accurate pinpointing of focal memory-related deficits will allow future targeted treatment for memory loss.

Gaze Fixation Patterns Correlate with Visual Attention and Memory: the Results of a Pilot Study in Healthy Subjects

“…At the third stage of the study, the subject could make mistakes in recognizing the previously seen objects and distinguishing between similar, new and previously seen objects. The situation of a false identification by the subject of a similar object as previously seen was regarded as a pattern separation error in agreement with the experience of other researchers [1][2][3][4].…”

“…The mechanisms of distinguishing between similar short-term memory traces (pattern separation) enable the ability of the brain to distinguish between similar ambient situations. In humans, this ability is tested in behavioral tasks of recognition of visually similar objects [1][2][3][4]. For example, when presented (with some time interval) with two similar images, a healthy individual imprints (memorizes) these images separately, which enables him/her to distinguish between them later.…”

“…In the recent decade, quite a few studies were devoted to these mechanisms in animals and humans [2][3][4][5][6][7]. In these research projects, the authors mainly described the mapping and localization of the pattern separation function throughout the hippocampus, the structure involved in the formation and extraction of new memories.…”

Sex hormones underlying 17a-Estradiol effects on neuroinflammation

“…A similar increase in age-associated gliosis is observed in CA3 after ovariectomy, but this hormonal effect is not apparent in DG. Each of these areas of the hippocampus has a distinctive function that is differentially affected by the brain aging process (Dillon et al 2017).…”

Phosphodiesterase inhibitors roflumilast and vardenafil prevent sleep deprivation‐induced deficits in spatial pattern separation

“…To be able to distinguish between overlapping information, the brain uses pattern separation, which is commonly defined as the ability to form separate representations from highly similar, yet slightly different events or stimuli (Yassa & Stark, ). Pattern separation occurs in the dentate gyrus (DG), a subregion of the hippocampus (Dillon et al, ; Yassa & Stark, ). Deficits in this process are among the first and most severe symptoms observed during aging and in disorders characterized by memory dysfunction such as Alzheimer's disease, post‐traumatic stress disorder, and schizophrenia.…”