Nobili L, Sannita W G
Department of Motor Sciences and Rehabilitation-Neurophysiopathology, University of Genoa, Italy.
Vision Res. 1997 Dec;37(24):3559-71. doi: 10.1016/S0042-6989(97)00076-X.
Electrophysiological evidence at a cellular level and in vivo macroelectrode recordings converge in indicating a degree of specificity of acetylcholine action in vision. Acetylcholine (ACh) function is also thought to play a significant role in memory, learning and other cognitive processes. In this respect, ACh action is suggested to serve in both sensory and cognitive processes. The pharmacological blocking of brain muscarinic transmission has been proposed as a model of geriatric memory impairment and Alzheimer's dementia. Visual electrophysiological testing is deemed of diagnostic specificity for this disease. ACh brain neurotransmission, however, mostly contributes to the modulation of nonspecific aspects of cognition, such as arousal or attention. Alzheimer's dementia results from complex neuron alterations [which also affect muscarinic receptors among other (sub)cellular structures] rather than simply reflecting ACh impoverishment. A substantial loss of retinal ganglion cells is documented in patients with Alzheimer's disease and is consistent with electrophysiological observations. However, it is unclear to what extent the dysfunction of the visual system observable in Alzheimer's dementia is qualitatively different from that occurring spontaneously during aging. The dissimilarities between the effect of acute muscarinic blocking (e.g. by scopolamine) and dementia outnumber the similarities. Accordingly, the conventional ACh agonist-antagonist model of dementia now appears questionable, and replacement treatment with compounds enhancing ACh function proved disappointing. It is suggested that (nonspecific) ACh action becomes function-specific, as determined by the architecture of local brain circuits in which it is involved.
细胞水平的电生理证据以及体内宏观电极记录均表明，乙酰胆碱在视觉方面的作用具有一定程度的特异性。乙酰胆碱（ACh）功能在记忆、学习及其他认知过程中也被认为发挥着重要作用。在这方面，乙酰胆碱的作用被认为在感觉和认知过程中均有体现。脑毒蕈碱传递的药理学阻断已被提出作为老年记忆障碍和阿尔茨海默病痴呆的模型。视觉电生理测试被认为对该疾病具有诊断特异性。然而，乙酰胆碱在脑内的神经传递主要有助于调节认知的非特异性方面，如觉醒或注意力。阿尔茨海默病痴呆是由复杂的神经元改变（这也会影响毒蕈碱受体以及其他细胞结构）导致的，而不仅仅是乙酰胆碱减少的反映。阿尔茨海默病患者视网膜神经节细胞大量丢失，这与电生理观察结果一致。然而，尚不清楚在阿尔茨海默病痴呆中可观察到的视觉系统功能障碍在何种程度上与衰老过程中自发出现的功能障碍在性质上有所不同。急性毒蕈碱阻断（如东莨菪碱）的效果与痴呆之间的差异多于相似之处。因此，传统的痴呆症乙酰胆碱激动剂 - 拮抗剂模型现在看来存在疑问，用增强乙酰胆碱功能的化合物进行替代治疗的效果也令人失望。有人提出，（非特异性的）乙酰胆碱作用会根据其所处的局部脑回路结构而变得具有功能特异性。
