Journal
CELL REPORTS
Volume 32, Issue 1, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2020.107864
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Funding
- Precursory Research for Embryonic Science and Technology (PRESTO) from the Japan Science and Technology Agency (JST) [JPMJPR12A1]
- KAKENHI grants from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japan Society for the Promotion of Science (JSPS) [24700403, 25116528, 26115530, 17H05985, 19H04942, 20H03550]
- Senshin Medical Research Foundation
- RIKEN, NIH grant [R01DA17310]
- KAKENHI [22110006, 16H01292, 18H05434, 25830023, 15H01571, 17H05695, 19K16293, 26870577, 15H04265, 26115504, 15H05723, 16H06536]
- Human Frontier Science Programme grant
- Fujitsu Laboratories
- program for Brain Mapping by Integrated Neurotechnolo-gies for Disease Studies (Brain/MINDS) from MEXT
- Japan Agency for Medical Research and Development (AMED)
- Regional Innovation Cluster Program grant (City Area Type, Central Saitama Area) from MEXT
- VW Foundation [ZN2632]
- BCCN [01GQ1005A, 01GQ1005B]
- DFG [CRC 1286, 889]
- Ministry for Science and Culture of Lower Saxony
- Max Planck Society
- [BES-2013-064171]
- [EEBB-I-15-09552]
- Grants-in-Aid for Scientific Research [20H03550, 19K16293, 19H04942, 22110006, 26115530, 26115504, 16H01292, 15H04265, 24700403, 25116528, 17H05985, 15H01571, 25830023, 26870577, 17H05695] Funding Source: KAKEN
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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.
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