Eckenstein F P, Baughman R W, Quinn J
Department of Neurobiology, Harvard Medical School, Boston, MA 02115.
Neuroscience. 1988 May;25(2):457-74. doi: 10.1016/0306-4522(88)90251-5.
The cholinergic innervation of rat cerebral cortex was studied by immunohistochemical localization of choline acetyltransferase. Stained bipolar cells, fibers and terminals were found in all areas of cortex. The density of cholinergic terminals was similar in all cortical areas with the exception of entorhinal and olfactory cortex, which showed a marked increase in the number of stained terminals. A laminar distribution of cholinergic terminals was found in many cortical areas. In motor and most sensory areas, terminal density was high in layer 1 and upper layer 5, and lowest in layer 4. Visual cortex, in contrast to other cortical areas, was characterized by a dense band of innervation in layer 4. It has been known that the majority of cortical cholinergic structures derive from a projection to cortex from large, multipolar neurons in the basal forebrain, which stain heavily for choline acetyltransferase. In this study, stained fibers were observed to take three different pathways from basal forebrain to cortex. The first, confined to medial aspects of forebrain and cortex, was observed to originate in the septal area, from where fibers formed a discrete bundle, swinging forward around the rostral end of the corpus callosum, then travelling caudally in the cingulate bundle. The second was found to consist of fibers fanning out laterally from the area of the globus pallidus, travelling through the caudate, then continuing for various distances in the corpus callosum before finally turning into the cortex. A third pathway appeared to innervate olfactory and entorhinal cortex. Ibotenic acid injections were made in the area of the globus pallidus to study the effect of lesioning the lateral pathway on the cholinergic innervation in cortex. A major loss of choline acetyltransferase positive terminals was observed in neocortex, but retrosplenial, cingulate, entorhinal and olfactory cortex showed a normal density of cholinergic innervation. The borders separating areas with lesioned cholinergic input from non-lesioned areas were precise. The distribution of stained terminals remaining in cortical areas with lesioned basal forebrain innervation suggests that the basal forebrain projection to cerebral cortex, and not the intrinsic cortical cholinergic neurons, give rise to the laminar distribution of cholinergic terminals observed in normal cortex. To compare the relative densities of different cholinergic cortical systems, the distribution of choline acetyltransferase staining was compared with that of vasoactive intestinal polypeptide and substance P, which are co-localized in some choline acetyltransferase-positive neurons innervating cortex.
通过胆碱乙酰转移酶的免疫组织化学定位研究了大鼠大脑皮质的胆碱能神经支配。在皮质的所有区域均发现了染色的双极细胞、纤维和终末。除内嗅皮质和嗅皮质外，所有皮质区域的胆碱能终末密度相似，内嗅皮质和嗅皮质的染色终末数量显著增加。在许多皮质区域发现了胆碱能终末的分层分布。在运动区和大多数感觉区，第1层和第5层上层的终末密度较高，第4层最低。与其他皮质区域不同，视皮质的特征是第4层有一条密集的神经支配带。已知大多数皮质胆碱能结构源自基底前脑的大型多极神经元向皮质的投射，这些神经元对胆碱乙酰转移酶染色很深。在本研究中，观察到染色纤维从基底前脑到皮质有三种不同的途径。第一种途径局限于前脑和皮质的内侧部分，观察到其起源于隔区，纤维从那里形成一个离散的束，围绕胼胝体的嘴端向前摆动，然后在扣带束中向尾侧走行。第二种途径发现由从苍白球区域向外扇形分布的纤维组成，穿过尾状核，然后在胼胝体中继续走行不同距离，最后进入皮质。第三条途径似乎支配嗅皮质和内嗅皮质。在苍白球区域注射鹅膏蕈氨酸以研究损伤外侧途径对皮质胆碱能神经支配的影响。在新皮质中观察到胆碱乙酰转移酶阳性终末大量丧失，但压后皮质、扣带皮质、内嗅皮质和嗅皮质的胆碱能神经支配密度正常。受损胆碱能输入区域与未受损区域之间的边界很清晰。在基底前脑神经支配受损的皮质区域中剩余的染色终末分布表明，基底前脑向大脑皮质的投射，而非皮质内源性胆碱能神经元，导致了正常皮质中观察到的胆碱能终末分层分布。为了比较不同胆碱能皮质系统的相对密度，将胆碱乙酰转移酶染色的分布与血管活性肠肽和P物质的分布进行了比较，血管活性肠肽和P物质共定位于一些支配皮质的胆碱乙酰转移酶阳性神经元中。
