@article{afa17bd2af7a40eea57b28844173b4ac,
title = "Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus",
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.",
keywords = "G-CaMP7, Shank, cognitive map, hippocampal CA1 region, memory, neurodevelopmental disorders, spatial learning, spatial navigation, synapses, two-photon imaging",
author = "Masaaki Sato and Kotaro Mizuta and Tanvir Islam and Masako Kawano and Yukiko Sekine and Takashi Takekawa and Daniel Gomez-Dominguez and Alexander Schmidt and Fred Wolf and Karam Kim and Hiroshi Yamakawa and Masamichi Ohkura and Lee, {Min Goo} and Tomoki Fukai and Junichi Nakai and Yasunori Hayashi",
note = "Funding Information: Y.H. was supported in part by Takeda Pharmaceutical and DWANGO. Funding Information: We thank Charles Yokoyama, Thomas J. McHugh, Shigeyoshi Fujisawa, Liset Menendez de la Prida, and Hokto Kazama for helpful comments and discussion. This work was supported by Precursory Research for Embryonic Science and Technology (PRESTO) JPMJPR12A1 from the Japan Science and Technology Agency (JST), KAKENHI grants 24700403 , 25116528 , 26115530 , 17H05985 , 19H04942 , and 20H03550 from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS), and a grant from the Senshin Medical Research Foundation to M.S.; RIKEN , NIH grant R01DA17310 , KAKENHI grants 22110006 , 16H01292 , and 18H05434 , a Human Frontier Science Programme grant, and Fujitsu Laboratories to Y.H.; KAKENHI grants 25830023 , 15H01571 , 17H05695 , and 19K16293 to K.M.; KAKENHI grant 26870577 to T.T.; KAKENHI grant 15H04265 to T.F; KAKENHI grants 26115504 , 15H05723 , and 16H06536 , and the program for Brain Mapping by Integrated Neurotechnologies for Disease Studies (Brain/MINDS) from MEXT and the Japan Agency for Medical Research and Development (AMED) to J.N.; Regional Innovation Cluster Program grant (City Area Type, Central Saitama Area) from MEXT to J.N. and M.O.; and grants from the VW Foundation ( ZN2632 ), BCCN ( 01GQ1005A and 01GQ1005B ), DFG ( CRC 1286 , 889 ), the Ministry for Science and Culture of Lower Saxony, and the Max Planck Society to F.W. D.G.-D. is a recipient of the PhD fellowship BES-2013-064171 and a grant from the short-term visit program EEBB-I-15-09552 . Publisher Copyright: {\textcopyright} 2020 The Authors",
year = "2020",
month = jul,
day = "7",
doi = "10.1016/j.celrep.2020.107864",
language = "English",
volume = "32",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "1",
}