Activity-dependent circuit formation in the neocortex

新皮质中活动依赖性回路的形成

• 批准号: 11680788
• 负责人: YAMAMOTO Nobuhiko
• 金额: $ 2.5万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11680788/
• 关键词: neocortex; horizontal axon; neuronal activity; organotypic culture; branching; synaptic transmission; rat; 大脳皮質; 分枝形成; 神経活動依存性; タイムラプス観察; スライス培養

In the developing visual cortex axons from upper layer cells travel along the same layers and form branches and synaptic connections. To date morphological and physiological studies have indicated that the formation of the horizontal connections is dependent on neuronal activity. However, how electrical activity influences branching of individual axons is not known. In addition, the molecular mechanisms underlying this process are almost unknown. We address this issue by using organotypic culture preparations of cortical slices. A new axon tracing method in which a small fraction of neurons are labeled with GFP was also developed. These methods enable us to observe individual axon arbors for a long period.In this study we have obatined the following results. First, axons from cortical cells in the upper layers formed branches in vitro in a fashion which is similar to that in vivo. Second, branching was accompanied by growth and retraction, suggesting that branch formation is a dynamic process. Third, branching was down-regulated when overall neuronal activity was suppressed by pharmacological treatments. Finally, the result suggests that RhoA, a small GTPase, is involved in intracellular mechanisms which convert electrical signals to the axon morphology.

在发育中的视觉皮层轴突中，来自上层细胞的轴突沿着同一层行进并形成分支和突触连接。迄今为止，形态学和生理学研究表明，水平连接的形成取决于神经元活动。然而，电活动如何影响单个轴突的分支尚不清楚。此外，这一过程背后的分子机制几乎是未知的。我们通过使用皮质切片的器官型培养制剂来解决这个问题。还开发了一种新的轴突追踪方法，其中一小部分神经元被 GFP 标记。这些方法使我们能够长期观察单个轴突乔木。在这项研究中，我们获得了以下结果。首先，上层皮层细胞的轴突在体外以与体内相似的方式形成分支。其次，分枝伴随着生长和收缩，表明分枝形成是一个动态过程。第三，当药物治疗抑制整体神经元活动时，分支会下调。最后，结果表明 RhoA（一种小型 GTP 酶）参与将电信号转换为轴突形态的细胞内机制。

项目成果

Yamamoto N.,Matsuyama Y.: "Charcterization of Fators Regulating Lamina-Specitic Growth"Journal of Neurobiology. 42. 56-68 (2000)

Yamamoto N.，Matsuyama Y.：“调节层特异性生长的因子的特征”神经生物学杂志。

Yamada K.,Yamamoto N.: "Development of Membrane properties of rat neocortical neurons"Neuroscience Letters. 275. 65-68 (1999)

Yamada K.，Yamamoto N.：“大鼠新皮质神经元膜特性的发展”神经科学快报。