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The impact of ageing reveals distinct roles for human dentate gyrus and CA3 in pattern separation and object recognition memory
Authors
A Bakker
AC Pereira
+41 more
AJ Mitchell
AM Brickman
AM Daugherty
AN Voineskos
B Wood
CJ Hodgetts
CQ Huang
CR Doxey
D Berron
D Marr
E Drapeau
HM Holden
IJ Bennett
JL Winterburn
JM Schott
LE Wisse
LE Wisse
M Jenkinson
M Ly
MA Kheirbek
MA Yassa
MA Yassa
MP Witter
MS Albert
N Raz
R Joie La
RM Baron
S Baker
S O’Mara
SA Small
SA Small
SG Mueller
SG Mueller
SL Leal
SM Stark
SM Stark
SM Stark
SN Burke
W Deng
Y Geinisman
ZM Reagh
Publication date
1 October 2017
Publisher
'Springer Science and Business Media LLC'
Doi
Cite
Abstract
© 2017 The Author(s). 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
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