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

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

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)


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.

Original languageEnglish
Article number107864
JournalCell Reports
Issue number1
Publication statusPublished - 2020 Jul 7
Externally publishedYes


  • G-CaMP7
  • Shank
  • cognitive map
  • hippocampal CA1 region
  • memory
  • neurodevelopmental disorders
  • spatial learning
  • spatial navigation
  • synapses
  • two-photon imaging

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)


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