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Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus

Authors
 Masaaki Sato  ;  Kotaro Mizuta  ;  Tanvir Islam  ;  Masako Kawano  ;  Yukiko Sekine  ;  Takashi Takekawa  ;  Daniel Gomez-Dominguez  ;  Alexander Schmidt  ;  Fred Wolf  ;  Karam Kim  ;  Hiroshi Yamakawa  ;  Masamichi Ohkura  ;  Min Goo Lee  ;  Tomoki Fukai  ;  Junichi Nakai  ;  Yasunori Hayashi 
Citation
 CELL REPORTS, Vol.32(1) : 107864, 2020-07 
Journal Title
CELL REPORTS
Issue Date
2020-07
MeSH
Anatomic Landmarks* ; Animals ; Behavior, Animal ; Cognition ; Female ; Goals ; Hippocampus / anatomy & histology* ; Hippocampus / cytology ; Male ; Mice, Transgenic ; Nerve Tissue Proteins / deficiency ; Nerve Tissue Proteins / metabolism ; Reward ; Task Performance and Analysis ; Time Factors
Keywords
G-CaMP7 ; Shank ; cognitive map ; hippocampal CA1 region ; memory ; neurodevelopmental disorders ; spatial learning ; spatial navigation ; synapses ; two-photon imaging
Abstract
In the hippocampus, locations associated with salient features are represented by a disproportionately large number of neurons, but the cellular and molecular mechanisms underlying this over-representation remain elusive. Using longitudinal calcium imaging in mice learning to navigate in virtual reality, we find that the over-representation of reward and landmark locations are mediated by persistent and separable subsets of neurons, with distinct time courses of emergence and differing underlying molecular mechanisms. Strikingly, we find that in mice lacking Shank2, an autism spectrum disorder (ASD)-linked gene encoding an excitatory postsynaptic scaffold protein, the learning-induced over-representation of landmarks was absent whereas the over-representation of rewards was substantially increased, as was goal-directed behavior. These findings demonstrate that multiple hippocampal coding processes for unique types of salient features are distinguished by a Shank2-dependent mechanism and suggest that abnormally distorted hippocampal salience mapping may underlie cognitive and behavioral abnormalities in a subset of ASDs.
Files in This Item:
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DOI
10.1016/j.celrep.2020.107864
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Lee, Min Goo(이민구) ORCID logo https://orcid.org/0000-0001-7436-012X
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/183867
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