Clarke D J, Nilsson O G, Brundin P, Björklund A
University Department of Pharmacology, Oxford, United Kingdom.
Exp Neurol. 1990 Jan;107(1):11-22. doi: 10.1016/0014-4886(90)90059-2.
The present experiment was performed to determine whether different types of grafted central cholinergic neurons are able to form synaptic contacts with host hippocampal neurons. Grafts from the septal-diagonal band area, which contain the neurons that normally innervate the hippocampal formation, were compared to those from the nucleus basalis magnocellularis region (NBM), the striatum, the pontomesencephalic tegmentum of the brain stem, and the spinal cord. The regions were dissected from 14- to 16-day-old rat fetuses, and the same number of viable cells (35 x 10(4] from each of the different regions was stereotaxically injected as a cell suspension into the hippocampus of rats subjected to a complete fimbria-fornix lesion, transecting the intrinsic septohippocampal pathways. At 14 to 17 weeks after transplantation, the brains were processed for choline acetyltransferase (ChAT) immunocytochemistry at the light and electron microscopic levels and acetylcholinesterase (AChE) histochemistry at the light microscopic level. There was a great variation in the number of surviving ChAT-positive cells among the different graft types. The septal grafts contained the highest number of ChAT-positive cells, and the striatal grafts showed the lowest numbers. The NBM, brain stem, and spinal cord grafts were in between. The differences in the number of ChAT-positive neurons between the groups matched, in general, the differences found in the magnitude of graft-derived AChE-positive fiber growth into the host hippocampal formation. At the electron microscopical level, all types of grafts were capable of forming synaptic contacts with host elements, however, with vast differences in the number of synapses found. The septal grafts produced the highest number of contacts, whereas the striatal and spinal cord grafts produced very few contacts. The ultrastructure of the cholinergic fibers from grafts obtained from the forebrain areas, i.e., septum, NBM, and striatum all appeared normal, whereas brain stem and spinal cord grafts produced different types of anomalies. The results show that grafted cholinergic neurons, that normally do not innervate the hippocampus, can send axons and form synaptic contacts in the host hippocampus. The ability to reinnervate the denervated hippocampal target appears to be shared by the embryologically closely related forebrain cholinergic neuron types, i.e., the septal, NBM, and striatal neurons. The marked differences in overall fiber ingrowth and number of synapses observed between these different types of grafts could be explained largely on the basis of differences in survivability of each grafted neuron type. By contrast, the reinnervation obtained from the grafted brain stem and spinal cord neurons were both quantitatively and qualitatively abnormal.(ABSTRACT TRUNCATED AT 400 WORDS)
本实验旨在确定不同类型移植的中枢胆碱能神经元是否能够与宿主海马神经元形成突触联系。将来自隔区 - 斜角带区域（该区域包含正常支配海马结构的神经元）的移植物与来自基底大细胞核区域（NBM）、纹状体、脑干脑桥中脑被盖以及脊髓的移植物进行比较。这些区域取自14至16日龄的大鼠胎儿，将相同数量的活细胞（来自每个不同区域的35×10⁴个）作为细胞悬液立体定向注射到接受完全穹窿 - 海马伞损伤（切断内在隔 - 海马通路）的大鼠海马中。移植后14至17周，对大脑进行处理，用于光镜和电镜水平的胆碱乙酰转移酶（ChAT）免疫细胞化学以及光镜水平的乙酰胆碱酯酶（AChE）组织化学检测。不同类型移植物中存活的ChAT阳性细胞数量存在很大差异。隔区移植物中ChAT阳性细胞数量最多，纹状体移植物中数量最少。NBM、脑干和脊髓移植物的数量介于两者之间。各组之间ChAT阳性神经元数量的差异总体上与移植物衍生的AChE阳性纤维向宿主海马结构生长的程度差异相匹配。在电镜水平上，所有类型的移植物都能够与宿主成分形成突触联系，然而，发现的突触数量差异很大。隔区移植物产生的突触数量最多，而纹状体和脊髓移植物产生的突触很少。来自前脑区域（即隔区、NBM和纹状体）的移植物中胆碱能纤维的超微结构均看起来正常，而脑干和脊髓移植物则产生了不同类型的异常。结果表明，通常不支配海马的移植胆碱能神经元能够在宿主海马中发出轴突并形成突触联系。胚胎学上密切相关的前脑胆碱能神经元类型（即隔区、NBM和纹状体神经元）似乎都具有重新支配去神经海马靶标的能力。在这些不同类型移植物之间观察到的总体纤维生长和突触数量的显著差异，在很大程度上可以基于每种移植神经元类型的存活能力差异来解释。相比之下，移植的脑干和脊髓神经元的重新支配在数量和质量上都是异常的。（摘要截断于400字）
