Studies of the mechanism generating left-right asymmetry of the brain

左右（L-R）不对称是高阶神经功能的基本特征。然而，大脑不对称的分子基础仍不清楚。我们最近报道了n -甲基- d -天冬氨酸受体（NMDAR）亚基GluRε2 （NR2B）在海马突触中的不同分配导致的海马回路的L-R不对称（Science, 2003）。ε1 （NR2A）敲除（KO）小鼠的研究。为了研究ε2的不对称分配是否与突触后细胞类型有关，我们比较了锥体细胞和中间神经元左、右突触中ε2的免疫金标记。为了便于检测ε2的密度差异，我们使用了具有简化的NMDA受体亚基组成的ε1亚基KO小鼠。我们发现ε2分布在左、右schi锥体细胞之间不对称，而在schi神经元间突触之间不对称，表明突触后细胞类型依赖于这种不对称的调节。我们还发现，在ε1亚基KO小鼠中，ε2分配的不对称性导致了NMDA受体含量和突触可塑性的左右差异（J. Neurosci, 2005）。静脉注射小鼠的研究。Iv是一种自发的小鼠突变体，具有编码运动蛋白的基因突变，左-右动力蛋白（Lrd）。50%的静脉/静脉注射小鼠表现出相反的位置，而其余的是正常的（孤立位置）。我们发现小鼠海马的突触分布ε2亚基呈右同分异构体。海马体的侧边性缺陷与内脏器官的侧边性无关。因此，在内脏器官和大脑之间，导致L-R不对称的机制是不同的（PLOS One, 2008）。

Left-right (L-R) asymmetry is a fundamental feature of higher-order neural function. However, the molecular basis of brain asymmetry remains unclear. We recently reported L-R asymmetry of hippocampal circuitry caused by differential allocation of N-methyl-D-aspartate receptor (NMDAR) subunit GluRε2 (NR2B) in hippocampal synapses (Science, 2003).Studies on ε1 (NR2A) knock-out (KO) mice. To investigate whether asymmetrical ε2 allocation is also related to the types of the postsynaptic cells, we compared postembedding immunogold labeling for ε2 in left and right Sch synapses on pyramidal cells and interneurons. To facilitate the detection of ε2 density difference, we used ε1 subunit KO mice, which have a simplified NMDA receptor subunit composition. We found that ε2 distribution was asymmetrical between left and right Sch-pyramidal cell but not Sch-interneuron synapses, indicating a postsynaptic cell-type dependent regulation of the asymmetry. Also, we found that, in ε1 subunit KO mice, the asymmetry of ε2 allocation results in left-right difference in NMDA receptor content and synaptic plasticity (J. Neurosci, 2005).Studies on iv mice. Iv is a spontaneous mouse mutant that possesses a mutation in the gene encoding the motor protein, Left-right dynein (Lrd). Fifty percent of iv/iv mice exhibit situs inversus, whereas the rest are normal (situs solitus). We found that the iv mouse hippocampus exhibited right isomerism of the synaptic distribution of the ε2 subunit. This laterality defect of the hippocampus is independent of the laterality of visceral organs. Therefore, the mechanisms responsible for the specification of L-R asymmetry differ between visceral organs and the brain (PLOS One, 2008).