Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits.
Mice lacking hippocampal left-right asymmetry show non-spatial learning deficits.
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缺乏海马左右不对称性的小鼠表现出非空间学习缺陷。
DOI：
10.1016/j.bbr.2017.08.043
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发表时间：
2018
影响因子：
2.7
通讯作者：
Watanabe S
中科院分区：
文献类型：
--
作者：
Shimbo A;Kosaki Y;Ito I;Watanabe S
已知左右不对称存在于大脑中的几个解剖水平，最近的研究提供了进一步的证据，表明它也存在于海马CA 3-CA 1回路的分子水平。N-甲基-d-天冬氨酸（NMDA）受体NR 2B亚单位在CA 1区锥体神经元的顶、基底突触中的分布是不对称的，如果输入来自左侧或右侧CA 3区锥体神经元。在本研究中，我们使用β2-微球蛋白基因敲除（β 2 m KO）小鼠（缺乏海马不对称性）研究海马不对称性在认知功能中的作用。我们在一系列空间和非空间学习任务中测试了β 2 m KO小鼠，并比较了β 2 m KO和C57 BL 6/J野生型（WT）小鼠的表现。β 2 m KO小鼠在空间参考记忆和空间工作记忆任务中均表现正常，但它们在学习两个非空间学习任务（即，较低行为率（DRL）任务和直线跑道任务的差异强化）。β 2 m KO小鼠在DRL任务中的反应时间也显示出较低的精确度，并且在直线跑道任务中的消退期间显示出较弱的自发恢复。这些结果表明，海马的不对称性是重要的非空间学习的某些特征。
Left-right asymmetry is known to exist at several anatomical levels in the brain and recent studies have provided further evidence to show that it also exists at a molecular level in the hippocampal CA3-CA1 circuit. The distribution of N-methyl-d-aspartate (NMDA) receptor NR2B subunits in the apical and basal synapses of CA1 pyramidal neurons is asymmetrical if the input arrives from the left or right CA3 pyramidal neurons. In the present study, we examined the role of hippocampal asymmetry in cognitive function using β2-microglobulin knock-out (β2m KO) mice, which lack hippocampal asymmetry. We tested β2m KO mice in a series of spatial and non-spatial learning tasks and compared the performances of β2m KO and C57BL6/J wild-type (WT) mice. The β2m KO mice appeared normal in both spatial reference memory and spatial working memory tasks but they took more time than WT mice in learning the two non-spatial learning tasks (i.e., a differential reinforcement of lower rates of behavior (DRL) task and a straight runway task). The β2m KO mice also showed less precision in their response timing in the DRL task and showed weaker spontaneous recovery during extinction in the straight runway task. These results indicate that hippocampal asymmetry is important for certain characteristics of non-spatial learning.