胼胝體是腦內(nèi)最大的聯(lián)合系統(tǒng),，由兩側(cè)大腦皮層錐體細(xì)胞發(fā)出的軸突集合而成，負(fù)責(zé)兩側(cè)大腦半球之間的信息交換。一個(gè)重要的問題是：從一側(cè)大腦皮層發(fā)出的胼胝體纖維是以怎樣的方式投射到對(duì)側(cè)皮層,？這種投射模式是受哪些因素調(diào)控的,？針對(duì)這些問題，中科院上海生命科學(xué)研究院丁玉強(qiáng)課題組的博士研究生王春雷和張磊等,，使用子宮內(nèi)電轉(zhuǎn)方法標(biāo)記大腦皮層軀體感覺區(qū)的錐體細(xì)胞,，持續(xù)穩(wěn)定表達(dá)的GFP 可以將這些神經(jīng)元發(fā)出的軸突顯示出來，從中可以觀察胼胝體整個(gè)發(fā)育過程,。
當(dāng)胼胝體軸突到達(dá)對(duì)側(cè)皮層后,，首先投射進(jìn)入第一體感區(qū)(S1)，然后進(jìn)入S1與第二體感區(qū)(S2)的交界處,。與S1區(qū)相比,，S1/S2交界處接受致密的胼胝體纖維投射，從而形成區(qū)域特異(region-specific)的投射特征,。進(jìn)入皮層的軸突主要分支中止在皮層的表面的2/3層,，形成層次特異(layer-specific)的投射特征。
這種區(qū)域和層次特異的投射方式是受神經(jīng)元電活動(dòng)(electrical activity)所調(diào)控的,。他們發(fā)現(xiàn),，在胼胝體神經(jīng)元內(nèi)過表達(dá)內(nèi)向整流性鉀通道(Kir2.1)降低胼胝體神經(jīng)元的電活動(dòng)后，胼胝體現(xiàn)纖維的區(qū)域和層次特異性投射方式發(fā)生明顯改變：S1/S2 交界處致密的投射纖維降低,，同時(shí)本應(yīng)中止在2/3層的軸突穿過2/3層而終止在最淺表的1層,。此外，當(dāng)轉(zhuǎn)染破傷風(fēng)毒素輕鏈(TeNT-LC)阻斷軸突末端的突觸傳遞后,，胼胝體纖維在S1/S2交界處的投射量下降更為顯著,，而后包括S1區(qū)和S1/S2交界的整個(gè)感覺皮層內(nèi)的胼胝體纖維消失。說明突觸傳遞對(duì)于胼胝體纖維的區(qū)域定位投射和其后的維持起著至關(guān)重要的作用,。這些結(jié)果表明,，在軀體感覺皮層，胼胝體軸突投射到對(duì)側(cè)皮層遵循區(qū)域和層次特異的投射方式,，并且這種投射方式受到神經(jīng)元活動(dòng)(神經(jīng)元電活動(dòng)和突觸傳遞)的調(diào)控,。另外，這項(xiàng)工作還確立了一個(gè)研究神經(jīng)軸突發(fā)育的新的在體研究系統(tǒng),。這一研究也得到了熊志奇和段樹民實(shí)驗(yàn)室的協(xié)助,。該項(xiàng)研究成果在線發(fā)表在10月17日出版的《神經(jīng)科學(xué)雜志》（The Journal of Neuroscience）上。（上海生命科學(xué)研究院）
原始出處:
The Journal of Neuroscience, October 17, 2007, 27(42):11334-11342; doi:10.1523/JNEUROSCI.3380-07.2007
Development/Plasticity/Repair
Activity-Dependent Development of Callosal Projections in the Somatosensory Cortex
Chun-Lei Wang, * Lei Zhang, * Yang Zhou, Jing Zhou, Xiu-Juan Yang, Shu-min Duan, Zhi-Qi Xiong, and Yu-Qiang Ding
Institute of Neuroscience and Key Laboratory of Neurobiology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Correspondence should be addressed to Dr. Yu-Qiang Ding, Institute of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China. Email: [email protected]
The corpus callosum is the largest commissural system in the mammalian brain, but the mechanisms underlying its development are not well understood. Here we report that neuronal activity is necessary for the normal development and maintenance of callosal projections in the mouse somatosensory cortex. We labeled a subpopulation of layer II/III callosal neurons via in utero electroporation and traced their axons in the contralateral cortex at different postnatal stages. Callosal axons displayed region- and layer-specific projection patterns within the first 2 weeks postnatally. Prenatal suppression of neuronal excitation was achieved via electroporation-induced overexpression of the inward rectifying potassium channel Kir2.1 in layer II/III cortical neurons. This resulted in abnormal callosal projections with many axons extending beyond layers II–III to terminate in layer I. Others failed to terminate at the border between the primary and secondary somatosensory cortices. Blocking synaptic transmission via expression of the tetanus toxin light chain (TeNT-LC) in these axons produced a more pronounced reduction in the projections to the border region, and the eventual disappearance of callosal projections over the entire somatosensory cortex. When Kir2.1 and TeNT-LC were coexpressed, callosal axon targeting exhibited a more severe phenotype that appeared to represent the addition of the effects produced by individual expression of Kir2.1 and TeNT-LC. These results underscore the importance of activity in regulating the developing neural connections and suggest that neuronal and synaptic activities are involved in regulating different aspects of the development of callosal projection.
Key words: corpus callosum; development; neuronal activity; somatosensory cortex; barrel cortex; synaptic transmission; Kir 2.1
