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一个基本特征。然而，大脑不对称的分子基础仍不清楚。我们最近报道了由于N-甲基-D-天冬氨酸受体(NMDAR)亚单位GluRε2(NR2B)在海马突触中的不同分布而引起的海马环路的不对称现象(《科学》，2003年)。ε1(NR2a)基因敲除(KO)小鼠的研究。为了研究ε2的不对称分布是否也与突触后细胞的类型有关，我们比较了包埋后免疫金标记法在锥体细胞和中间神经元的左右SCH突触中对ε2的标记。为了便于检测ε-2密度差异，我们使用了ε-1亚单位KO小鼠，它们具有简化的NMDA受体亚单位组成。我们发现ε-2在左右脊髓锥体细胞之间的分布是不对称的，但在脊髓神经元间突触之间没有分布，这表明这种不对称是突触后细胞类型的调节。此外，我们还发现，在ε1亚单位KO小鼠中，ε2分配的不对称性导致了NMDAD受体含量和突触可塑性的左右差异(J.Neurosci，2005年)。IV是一种自发突变的小鼠，编码运动蛋白左-右动力蛋白(LRd)的基因发生突变。在iv/iv小鼠中，有50%的小鼠出现内翻，而其余小鼠的内翻是正常的。我们发现，iv小鼠海马区的ε-2亚单位的突触分布呈现右异构性。海马体的这种偏侧性缺陷与内脏器官的偏侧性无关。因此，导致L-R不对称性的机制在内脏器官和脑中不同(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).