THE FOREBRAIN CHOLINERGIC SYSTEM IN HEALTH AND DISEASE

一些证据表明，大的胆碱能神经元， 前脑胆碱能（Ch）系统，其投射到杏仁核、海马， 和新皮层，在脑电图的神经机制中发挥作用 (EEG)激活、学习和记忆。 此外，有人建议， Ch系统中的损伤可能是造成某些记忆的原因， 衰老的功能障碍，严重的胆碱能缺乏可能是 在阿尔茨海默病（AD）痴呆的发病机制中起重要作用 和阿尔茨海默型老年性痴呆（SDAT）。 如果我们要 了解这个系统在老年记忆功能障碍中的作用， AD痴呆，组织和功能特性的知识， Ch系统至关重要。 阐明Ch系统在以下方面的作用： 健康，衰老和疾病，我们将使用免疫细胞化学和 组织化学方法，计算机辅助形态计量学研究，逆行 和顺行转运技术，[3 H]配体受体放射自显影， 发射器特异性酶的测定，单位记录，微刺激， EEG和各种行为测试，以评估Ch系统：正常 大鼠和非人灵长类动物; Ch选择性病变的动物 系统;和非人灵长类动物显示年龄相关的功能和 结构异常，包括记忆功能障碍和神经炎 斑块 病变动物和老龄动物将被评估为潜在 用于评价改善功能的药理学策略的模型 CH系统。 这些多学科的方法， 为了澄清Ch系统的结构和功能，如果 我们需要了解胆碱能和其他 衰老临床表现中的特异性递质异常 AD/SDAT。 只有通过了解正常和不正常的生物学， 我们可以期望设计合理的方法来处理这些过程， 这些神经系统疾病影响着我们社会中的许多人。

Several lines of evidence suggest that large cholinergic neurons of the forebrain cholinergic (Ch) system, which project to amygdala, hippocampus, and neocortex, play a role in the neural mechanisms of electroencephalogram (EEG) activation, learning, and memory. Moreover, it has been suggested that impairments in the Ch system may be responsible for some of the memory dysfunctions in aging and that severe cholinergic deficiencies may be important in the pathogenesis of the dementia of Alzheimer's disease (AD) and senile dementia of the Alzheimer's type (SDAT). If we are to understand the roles of this system in the geriatric memory dysfunction and dementia of AD, knowledge of the organization and functional properties of the Ch system is essential. To clarify the roles of the Ch system in health, aging, and disease, we will use immunocytochemical and histochemical methods, computer-assisted morphometric studies, retrograde and anterograde transport techniques, [3H] ligand receptor autoradiography, assays of transmitter-specific enzymes, unit recordings, microstimulation, EEG, and a variety of behavioral tests to assess the Ch system in: normal rats and nonhuman primates; animals with selective lesions of the Ch system; and nonhuman primates showing age-associated functional and structural abnormalities, including memory dysfunction and neuritic plaques. Lesioned animals and aged animals will be assessed as potential models for evaluating pharmacological strategies to improve the functions of the Ch system. These multidisciplinary approaches, which are designed to clarify the structure and functions of the Ch system, are essential if we are to understand the contributions of cholinergic and other transmitter-specific abnormalities in the clinical manifestations of aging and AD/SDAT. Only by understanding the normal and abnormal biology of these processes can we expect to design rational approaches to deal with these neurological disorders that affect so many individuals in our society.