日前,，復旦大學神經(jīng)生物學研究所禹永春課題組與美國紐約斯隆凱特琳癌癥研究中心時松海課題組合作，在腦神經(jīng)環(huán)路發(fā)育研究中,，首次發(fā)現(xiàn)腦神經(jīng)元間由電突觸介導的信息交流在大腦皮層神經(jīng)環(huán)路發(fā)育中有重要作用,，相關(guān)研究成果于5月3日在線發(fā)表在國際期刊《自然》（Nature）雜志上。
電突觸被普遍認為在神經(jīng)元相互信息交流中具有重要作用,。研究表明,，在哺乳動物大腦皮層發(fā)育早期興奮性神經(jīng)元之間，存在著大量的電突觸,。然而,，隨著大腦皮層不斷發(fā)育，神經(jīng)元間電突觸聯(lián)系逐漸消失,，取而代之的是化學性突觸,。
到目前為止，人們對化學性突觸研究有所深入,，但對電突觸在腦皮層神經(jīng)環(huán)路發(fā)育中發(fā)揮的作用卻知之甚少,。
禹永春等通過改變興奮性神經(jīng)元間電突觸傳遞的方法，首次探明了電突觸在腦皮層神經(jīng)環(huán)路發(fā)育中的重要作用,，即神經(jīng)元間電突觸的信息交流為“進化”到化學性突觸聯(lián)系提供了重要的準備,。
為了更進一步研究電突觸對化學性突觸發(fā)育的影響，禹永春等巧妙地利用分子生物學的方法,，選擇性地關(guān)閉姐妹神經(jīng)元電突觸通道,。他們發(fā)現(xiàn),，通道關(guān)閉后，姐妹神經(jīng)元之間的化學突觸聯(lián)系顯著下降,，但是非姐妹神經(jīng)元之間的化學突觸聯(lián)系沒有受到影響,。
研究結(jié)果表明，大腦皮層神經(jīng)環(huán)路發(fā)育是有一定規(guī)律的,，即神經(jīng)元親緣性越高越容易形成神經(jīng)突觸聯(lián)系。更為重要的是,，神經(jīng)元親緣性是由電突觸聯(lián)系在一起的。“該成果首次揭示了電突觸和化學突觸之間的因果聯(lián)系,，在大腦皮層發(fā)育過程中,，如果沒有電突觸就不會形成化學突觸。”
有關(guān)專家認為,，該研究不僅為科學家深入研究大腦皮層神經(jīng)網(wǎng)絡(luò)形成之謎提供了重要啟示,，同時也為腦神經(jīng)環(huán)路發(fā)育異常相關(guān)疾病，如小兒癲癇,、自閉癥、智力發(fā)育遲滯等的診斷和治療提供了新思路和新靶點,。（生物谷Bioon.com）
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.
