Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus
Distinct Mechanisms of Over-Representation of Landmarks and Rewards in the Hippocampus
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DOI：
10.1016/j.celrep.2020.107864
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发表时间：
2020-07-07
期刊：
影响因子：
8.8
通讯作者：
Hayashi, Yasunori
中科院分区：
文献类型：
--
作者：
Sato, Masaaki;Mizuta, Kotaro;Hayashi, Yasunori
在海马体中，与显着特征相关的位置由数量过多的神经元代表，但这种过度代表背后的细胞和分子机制仍然难以捉摸。在学习虚拟现实导航的小鼠中使用纵向钙成像，我们发现奖励和标志位置的过度表达是由持久且可分离的神经元子集介导的，具有不同的出现时间过程和不同的潜在分子机制。引人注目的是，我们发现在缺乏Shank2（一种编码兴奋性突触后支架蛋白的自闭症谱系障碍（ASD）相关基因）的小鼠中，学习诱导的标志物过度表现不存在，而奖励的过度表现则大幅增加，目标导向行为也是如此。这些发现表明，独特类型的显着特征的多个海马编码过程通过 Shank2 依赖性机制来区分，并表明异常扭曲的海马显着性映射可能是 ASD 子集认知和行为异常的基础。
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.