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

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. [Display omitted] •CA1 over-representation of reward and landmark emerge with distinct time courses•These cells form stable singularities during experience-dependent map consolidation•The over-representation of landmark but not reward is dependent on Shank2 Using longitudinal two-photon calcium imaging in mice during virtual navigation, Sato et al. demonstrate that persistent and separable neuronal subsets mediate the hippocampal over-representation of reward and landmark locations. Learning-induced over-representation of landmarks is absent while rapid over-representation of rewards is enhanced, in a mouse model of autism lacking Shank2.