Effects of Selective Acetylcholine Loss on Experience-Dependent Plasticity

哺乳动物的躯体感觉皮层以其对身体对触摸有反应的部位的地图式表示而闻名。 这个区域也是最早被用来显示现在被称为经验依赖性可塑性的共同皮层特性的区域之一，这是皮层对特定空间刺激的敏感性的变化。 如果身体的一个区域长时间被剥夺触摸，皮质中的反应区域变得不那么敏感，并且可能会减少;如果身体的区域被持续刺激，皮质敏感性增加，皮质区域可能会扩大。 一个简单的模型系统显示的可塑性是面部胡须阵列的啮齿动物，它映射在一个非常独特的方式在什么是所谓的“桶场”的形状。 长的胡须可以很容易地每天修剪，因此完整的胡须比修剪的胡须接受更多的自然感觉刺激，并且事实证明，对邻近修剪的胡须与未修剪的胡须的中枢反应显示出显着的变化。 该项目研究了一种称为乙酰胆碱（ACh）的生化化合物在经验依赖性可塑性中的作用。 已知乙酰胆碱会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阻断来自大脑一部分的乙酰胆碱输入，该部分是乙酰胆碱输入皮层的主要来源。 电生理记录测量中枢皮层神经细胞的反应性，以定量分析有和没有精确和特异性ACh阻断的可塑性。 结果将是重要的理解皮质功能的性质，并具有潜在的影响，不仅从皮质缺损的恢复，而且对发展的机制，也许学习。

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.