Mrzljak L, Pappy M, Leranth C, Goldman-Rakic P S
Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
J Comp Neurol. 1995 Jul 10;357(4):603-17. doi: 10.1002/cne.903570409.
Surprisingly little is known about the synaptic architecture of the cholinergic innervation in the primate cerebral cortex in spite of its acknowledged relevance to cognitive processing and Alzheimer's disease. To address this knowledge gap, we examined serially sectioned cholinergic axons in supra- and infragranular layers of the macaque prefrontal cortex by using an antibody against the acetylcholine synthesizing enzyme, choline acetyltransferase (ChAT). The tissue bound antibody was visualized with both immunoperoxidase and silver-enhanced diaminobenzidine sulfide (SEDS) techniques. Both methods revealed that cholinergic axons make synapses in all cortical layers and that these synapses are exclusively symmetric. Cholinergic axons formed synapses primarily on dendritic shafts (70.5%), dendritic spines (25%), and, to a lesser extent, cell bodies (4.5%). Both pyramidal neurons and cells exhibiting the morphological features of GABAergic cells were targets of the cholinergic innervation. Some spiny dendritic shafts received multiple, closely spaced synapses, suggesting that a subset of pyramidal neurons may be subject to a particularly strong cholinergic influence. Analysis of synaptic incidence of cholinergic profiles in the supragranular layers of the prefrontal cortex by the SEDS technique revealed that definitive synaptic junctions were formed by 44% of the cholinergic boutons. An unexpected finding was that cholinergic boutons were frequently apposed to spines and small dendrites without making any visible synaptic specializations. These same spines and dendrites often received asymmetric synapses, presumably of thalamocortical or corticocortical origin. Present ultrastructural findings suggest that acetylcholine may have a dual modulatory effect in the neocortex: one through classical synaptic junctions on dendritic shafts and spines, and the other through nonsynaptic appositions in close vicinity to asymmetric synapses. Further physiological studies are necessary to test the hypothesis of the nonsynaptic release of acetylcholine in the cortex.
尽管人们已经认识到灵长类动物大脑皮层中胆碱能神经支配的突触结构与认知加工及阿尔茨海默病相关，但令人惊讶的是，目前对此了解甚少。为了填补这一知识空白，我们使用针对乙酰胆碱合成酶——胆碱乙酰转移酶（ChAT）的抗体，检查了猕猴前额叶皮层颗粒上层和颗粒下层中连续切片的胆碱能轴突。通过免疫过氧化物酶和银增强硫化二氨基联苯胺（SEDS）技术对与组织结合的抗体进行可视化处理。两种方法均显示，胆碱能轴突在所有皮层层形成突触，且这些突触均为对称性突触。胆碱能轴突主要在树突干（70.5%）、树突棘（25%）上形成突触，在较小程度上也在细胞体（4.5%）上形成突触。锥体细胞和具有GABA能细胞形态特征的细胞都是胆碱能神经支配的靶点。一些有棘的树突干接受多个紧密排列的突触，这表明一部分锥体细胞可能受到特别强烈的胆碱能影响。通过SEDS技术分析前额叶皮层颗粒上层中胆碱能轮廓的突触发生率，结果显示44%的胆碱能终扣形成了明确的突触连接。一个意外的发现是，胆碱能终扣经常与树突棘和小树突相邻，但未形成任何可见的突触特化结构。这些相同的树突棘和树突经常接受不对称突触，推测其起源于丘脑皮质或皮质皮质。目前的超微结构研究结果表明，乙酰胆碱可能在新皮层中具有双重调节作用：一种是通过在树突干和树突棘上的经典突触连接，另一种是通过在不对称突触附近的非突触毗邻。需要进一步的生理学研究来验证皮层中乙酰胆碱非突触释放的假说。
