Effects of Selective Acetylcholine Loss on Experience-Dependent Plasticity

哺乳动物的体感皮层以其对触摸做出反应的身体部位的地图状表示而闻名。这个区域也是第一个被用来展示现在被称为经验依赖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反应敏感性的变化。如果身体的某个部位长时间失去触觉，大脑皮层的反应区域就会变得不那么敏感，甚至可能会减少；如果身体的这个区域持续受到刺激，皮质的敏感性会增加，皮质的面积可能会扩大。展示这种可塑性的一个简单的模型系统是啮齿类动物的面部须阵列，它们以一种非常独特的方式在形状上被称为“桶域”。长须易于日常修剪，因此完整的须比修剪过的须接受更多的自然感官刺激，并且对相邻修剪过的须和未修剪过的须的中枢反应有显著的变化。这个项目研究了一种叫做乙酰胆碱（ACh）的生化化合物在经验依赖可塑性中的作用。已知乙酰胆碱能影响神经细胞间兴奋性冲动的传递。一种新的特异性免疫毒素被用于从药理学上阻断乙酰胆碱从大脑的一部分，提供乙酰胆碱输入的主要来源皮质。电生理记录测量中枢皮质神经细胞的反应性，定量分析有或没有精确和特异性乙酰胆碱阻断的可塑性。研究结果对于理解皮质功能的本质具有重要意义，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.