Role of Activity in Refinement of Synaptic Connections

这个项目的目标是了解发育中的神经细胞是如何与肌肉建立联系的，并确定这些联系是如何随着活动而改变其特性的。有证据表明，发育中的神经连接在发育过程中通过活动调节机制得到改善。活动对神经末梢大小和投射模式变化的影响将通过突变来检验，突变破坏了神经元和肌肉产生正常电活动的能力。这些变化也将通过使用专门干扰神经和肌肉电活动的毒素来调查。为了观察神经肌肉连接的发育及其对实验操作的反应，将制作半完整培养中保持的活神经末梢的延时视频电影。这些实验将阐明正常神经系统发育的几个基本特征。

The goal of this project is to understand how developing nerve cells make connections with muscles, and to determine how those connections alter their properties as a function of activity. There is evidence that developing nerve connections are refined during development by activity mediated mechanisms. The influence of activity on changes in nerve ending size and projection patterns will be examined by use of mutations that disrupt the ability of neurons and muscles to generate normal electrical activity. These changes will also be investigated by the use of toxins that specifically interfere with nerve and muscle electrical activity. To observe the development of the nerve muscle connections, and their responses to experimental manipulations, time-lapse video movies will be made of the living nerve endings maintained in semi- intact cultures. These experiments will elucidate several fundamental features of normal nervous system development.