Effects of Selective Acetylcholine Loss on Experience-Dependent Plasticity

哺乳动物的体感皮层以其对身体对触摸作出反应的部位的地图状表现而闻名。这一区域也是最早被用来显示一种现在被称为经验依赖性可塑性的常见皮质属性的区域之一，这是大脑皮质对特定空间刺激反应的敏感度的变化。如果身体的一个区域长时间被剥夺接触，皮质的响应区就会变得不那么敏感，可能会减少；如果身体的某个区域受到持续的刺激，皮质敏感度会增加，皮质面积可能会扩大。展示可塑性的一个简单的模型系统是啮齿动物的面部胡须阵列，它以一种非常独特的方式绘制出因其形状而被称为“桶形场”的区域。长胡须可以很容易地每天修剪，因此完整的胡须比修剪过的胡须获得更多的自然感觉刺激，事实证明，对邻近修剪过的胡须和未修剪的胡须的中央反应显示出显著的变化。本项目研究一种名为乙酰胆碱(ACh)的生化化合物在经验依赖性可塑性中的作用。已知ACh影响神经细胞之间兴奋性冲动的传递。一种新的特异性免疫毒素被用来从药物上阻断来自大脑某一部分的ACh输入，该部分为大脑皮质提供ACh输入的主要来源。电生理记录测量中央皮质神经细胞的反应性，以定量分析在有或没有准确和特异的ACh阻断的情况下的可塑性。研究结果将对理解皮质功能的本质很重要，不仅对皮质缺陷的恢复有潜在的影响，而且对发育和学习的机制也有潜在的影响。

The somatosensory cortex of mammals is famous for its map-like representation of the parts of the body responsive to touch. This area also was one of the first used to show what is now known as a common cortical property called experience-dependent plasticity, which is a change in the sensitivity of cortical responses to a particular spatial stimulus. If an area of the body is deprived of touch for a long time, the responsive area in the cortex becomes less sensitive and may decrease; if the area of the body is continually stimulated, the cortical sensitivity increases and the cortical area may expand. A simple model system for showing the plasticity is the facial whisker array of rodents, which maps in a very distinctive way in what are called "barrel fields" for their shape. The long whiskers easily can be trimmed daily, so that the intact whiskers receive much more of natural sensory stimulation than the trimmed ones, and it turns out that the central responses to neighboring trimmed versus untrimmed whiskers show significant changes. This project investigates the role of a biochemical compound called acetylcholine (ACh) in the experience-dependent plasticity. ACh is known to affect the transmission of excitatory impulses between nerve cells. A novel specific immunotoxin is used to pharmacologically block ACh inputs from a part of the brain that provides the major source of ACh inputs to the cortex. Electrophysiological recordings measure the responsiveness of central cortical nerve cells to give a quantitative assay of the plasticity with and without the precise and specific ACh blockage. Results will be important to understanding the nature of cortical function, and have potential impact not only on recovery from cortical deficits, but also on mechanisms of development and perhaps learning.