Nature：禹永春等脑神经环路发育研究获重要进展

日前，复旦大学神经生物学研究所禹永春课题组与美国纽约斯隆凯特琳癌症研究中心时松海课题组合作，在脑神经环路发育研究中，首次发现脑神经元间由电突触介导的信息交流在大脑皮层神经环路发育中有重要作用，相关研究成果于5月3日在线发表在国际期刊《自然》（Nature）杂志上。

电突触被普遍认为在神经元相互信息交流中具有重要作用。研究表明，在哺乳动物大脑皮层发育早期兴奋性神经元之间，存在着大量的电突触。然而，随着大脑皮层不断发育，神经元间电突触联系逐渐消失，取而代之的是化学性突触。

到目前为止，人们对化学性突触研究有所深入，但对电突触在脑皮层神经环路发育中发挥的作用却知之甚少。

禹永春等通过改变兴奋性神经元间电突触传递的方法，首次探明了电突触在脑皮层神经环路发育中的重要作用，即神经元间电突触的信息交流为“进化”到化学性突触联系提供了重要的准备。

为了更进一步研究电突触对化学性突触发育的影响，禹永春等巧妙地利用分子生物学的方法，选择性地关闭姐妹神经元电突触通道。他们发现，通道关闭后，姐妹神经元之间的化学突触联系显著下降，但是非姐妹神经元之间的化学突触联系没有受到影响。

研究结果表明，大脑皮层神经环路发育是有一定规律的，即神经元亲缘性越高越容易形成神经突触联系。更为重要的是，神经元亲缘性是由电突触联系在一起的。“该成果首次揭示了电突触和化学突触之间的因果联系，在大脑皮层发育过程中，如果没有电突触就不会形成化学突触。”

有关专家认为，该研究不仅为科学家深入研究大脑皮层神经网络形成之谜提供了重要启示，同时也为脑神经环路发育异常相关疾病，如小儿癫痫、自闭症、智力发育迟滞等的诊断和治疗提供了新思路和新靶点。

doi:10.1038/nature10958
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Preferential electrical coupling regulates neocortical lineage-dependent microcircuit assembly

Yong-Chun Yu Shuijin He She Chen Yinghui Fu Keith N. Brown Xing-Hua Yao Jian Ma1 Kate P. Gao Gina E. Sosinsky Kun Huang Song-Hai Shi

Radial glial cells are the primary neural progenitor cells in the developing neocortex1. Consecutive asymmetric divisions of individual radial glial progenitor cells produce a number of sister excitatory neurons that migrate along the elongated radial glial fibre, resulting in the formation of ontogenetic columns2, 3, 4. Moreover, sister excitatory neurons in ontogenetic columns preferentially develop specific chemical synapses with each other rather than with nearby non-siblings5. Although these findings provide crucial insight into the emergence of functional columns in the neocortex, little is known about the basis of this lineage-dependent assembly of excitatory neuron microcircuits at single-cell resolution. Here we show that transient electrical coupling between radially aligned sister excitatory neurons regulates the subsequent formation of specific chemical synapses in the neocortex. Multiple-electrode whole-cell recordings showed that sister excitatory neurons preferentially form strong electrical coupling with each other rather than with adjacent non-sister excitatory neurons during early postnatal stages. This preferential coupling allows selective electrical communication between sister excitatory neurons, promoting their action potential generation and synchronous firing. Interestingly, although this electrical communication largely disappears before the appearance of chemical synapses, blockade of the electrical communication impairs the subsequent formation of specific chemical synapses between sister excitatory neurons in ontogenetic columns. These results suggest a strong link between lineage-dependent transient electrical coupling and the assembly of precise excitatory neuron microcircuits in the neocortex.