A study of mechanisms for formation of thalamocortical projectic

丘脑皮质投射形成机制的研究

基本信息

批准号：
09680793
负责人：
YAMAMOTO Nobuhiko
金额：
$ 2.11万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

项目摘要

In the development of the brain axons stop growing and form branches upon reaching their targets.The thalamocortical connection is a suitable system for studying this issue, because sensory thalamic axons project primarily to layer 4 of the neocortex, which is well characterized by cytoarchitectonic structure.To date developmental studies have suggested that thalamic axons can recognize the target layer through lamina-specific cues in the cortex, but the molecular mechanism has almost remained unknown.We attempted to reveal characteristics of possible factors that are responsible for layer-specific termination and branching of thalamocortical axons.For that purpose, axonal extension from rat embryonic thalamus on postnatal neocortical slices which had been fixed chemically was used as an experimental model system.Under these conditions the role of membrane-bound components can be analyzed without contamination of soluble factors released from cortical tissues.Thalamic axons extended even on fixed cortex and exhibited farther growth in the deep layers (layers 5 and 6) than the upper layers (layers 1 through 4).Enzymatic treatment to cortical slices prior to culturing further demonstrated that the laminar difference in axonal outgrowth was primarily due to PI-PLC-sensitive components which are present in the upper layers.On the other hand, axonal branching occurred mostly in layer 4 of the fixed cortical slices.This laminar localization of branch formation was slightly weakened in neuraminidase-treated cortical slices with an increase in the number of branches.These findings suggest that GPI- anchored and sialic acid-containing molecules regulate layer-specific thalamic axon growth and branch formation, respectively, through inhibitory activity.

在达到目标时，脑轴突的发展停止生长并形成分支。丘脑皮层连接是研究此问题的合适系统，因为感觉丘脑轴突主要针对新皮层的第4层，其特征在于细胞构造结构。迄今为止，发育研究表明，丘脑轴突可以通过皮质中的椎板特异性提示识别目标层，但是分子机制几乎尚不清楚。我们试图揭示导致层特异性终止和分支的可能因素的特征为此目的，从大鼠胚胎丘脑延伸到产后新皮层切片上的轴突延伸，该切片已被化学固定为实验模型系统。在这些条件下，可以分析膜结合的成分的作用，而无需释放可溶性因子释放的可溶性因子的作用丘脑轴突甚至在固定皮质上延伸，并在深层（5和6层）中表现出更远的生长（层1至4）。在轴突产物中，主要是由于上层中存在的PI-PLC敏感成分。另一方面，轴突分支主要发生在固定皮质切片的第4层中 - 经过分支数量增加的经过处理的皮质切片。这些发现表明，含有GPI的含唾液酸和唾液酸的分子分别通过抑制活性调节了层特异性的丘脑轴突生长和分支形成。