胼胝体是脑内最大的联合系统，由两侧大脑皮层锥体细胞发出的轴突集合而成，负责两侧大脑半球之间的信息交换。一个重要的问题是：从一侧大脑皮层发出的胼胝体纤维是以怎样的方式投射到对侧皮层？这种投射模式是受哪些因素调控的？针对这些问题，中科院上海生命科学研究院丁玉强课题组的博士研究生王春雷和张磊等，使用子宫内电转方法标记大脑皮层躯体感觉区的锥体细胞，持续稳定表达的GFP 可以将这些神经元发出的轴突显示出来，从中可以观察胼胝体整个发育过程。
当胼胝体轴突到达对侧皮层后，首先投射进入第一体感区(S1)，然后进入S1与第二体感区(S2)的交界处。与S1区相比，S1/S2交界处接受致密的胼胝体纤维投射，从而形成区域特异(region-specific)的投射特征。进入皮层的轴突主要分支中止在皮层的表面的2/3层，形成层次特异(layer-specific)的投射特征。
这种区域和层次特异的投射方式是受神经元电活动(electrical activity)所调控的。他们发现，在胼胝体神经元内过表达内向整流性钾通道(Kir2.1)降低胼胝体神经元的电活动后，胼胝体现纤维的区域和层次特异性投射方式发生明显改变：S1/S2 交界处致密的投射纤维降低，同时本应中止在2/3层的轴突穿过2/3层而终止在最浅表的1层。此外，当转染破伤风毒素轻链(TeNT-LC)阻断轴突末端的突触传递后，胼胝体纤维在S1/S2交界处的投射量下降更为显著，而后包括S1区和S1/S2交界的整个感觉皮层内的胼胝体纤维消失。说明突触传递对于胼胝体纤维的区域定位投射和其后的维持起着至关重要的作用。这些结果表明，在躯体感觉皮层，胼胝体轴突投射到对侧皮层遵循区域和层次特异的投射方式，并且这种投射方式受到神经元活动(神经元电活动和突触传递)的调控。另外，这项工作还确立了一个研究神经轴突发育的新的在体研究系统。这一研究也得到了熊志奇和段树民实验室的协助。该项研究成果在线发表在10月17日出版的《神经科学杂志》（The Journal of Neuroscience）上。（上海生命科学研究院）
原始出处:
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: dingyq@ion.ac.cn
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
