Freund T F, Bolam J P, Björklund A, Stenevi U, Dunnett S B, Powell J F, Smith A D
J Neurosci. 1985 Mar;5(3):603-16. doi: 10.1523/JNEUROSCI.05-03-00603.1985.
In adult rats with a unilateral 6-hydroxydopamine-induced destruction of the nigrostriatal dopamine (DA) pathway, grafts of embryonic substantia nigra can establish a new dopaminergic terminal fiber plexus in the previously denervated neostriatum and compensate for some of the behavioral deficits induced by the nigrostriatal lesion. In the present study the synaptic connections of the ingrowing DA fibers from the graft were analyzed ultrastructurally, using immunocytochemical localization of tyrosine hydroxylase (TH), in animals whose lesion-induced motor asymmetry had been completely compensated for by the nigral grafts. In two of the animals, horseradish peroxidase-wheatgerm agglutinin conjugate was injected into the graft in order to trace possible reciprocal afferent connections to the graft from the host striatum. TH-immunoreactive axons from the graft were seen to make abundant symmetric synapses with neuronal elements in the host neostriatum. Between 85 and 90% of these synapses were on dendritic shafts and spines, and the rest were on neuronal perikarya. Two principal targets were identified: dendrites of spiny neurons, the majority of which are likely to be striatal projection neurons; and the cell bodies of giant neurons, most (or perhaps all) of which are known to be cholinergic interneurons. The synapses made on dendritic spines, which constituted about 40% of all TH-positive synapses formed by the TH-positive neurons in the graft, resembled those seen in normal animals, both in that they made contacts with spine necks and in that they invariably were associated with an asymmetric TH-negative synapse contacting the spine head. The innervation of the giant cell perikarya, which constituted about 6% of all TH-positive synapses found, was strikingly abnormal in that the graft-derived TH-positive fibers formed dense pericellular "baskets" selectively around the giant cell bodies. Such arrangements were never seen in the normal striatum, nor did they occur in the intact contralateral striatum in the grafted animals. It is proposed that this apparent dopaminergic hyperinnervation from the graft could provide a powerful inhibition of the cholinergic interneurons in the reinnervated host striatum, and that such an inhibitory mechanism could assist in the graft-induced functional recovery by potentiating the functional effects of DA synapses terminating on the spiny efferent neurons. This dual innervation may thus help to explain why restoration of only a small proportion of the striatal DA innervation by the graft is sufficient to induce complete compensation of, e.g., motor asymmetry in the lesioned rats.(ABSTRACT TRUNCATED AT 400 WORDS)
在成年大鼠中，单侧6-羟基多巴胺诱导黑质纹状体多巴胺（DA）通路受损，胚胎黑质移植能够在先前去神经支配的新纹状体中建立新的多巴胺能终末纤维丛，并补偿黑质纹状体损伤所诱发的一些行为缺陷。在本研究中，利用酪氨酸羟化酶（TH）的免疫细胞化学定位，对移植的DA纤维向内生长形成的突触连接进行了超微结构分析，实验动物的损伤诱导运动不对称已完全由黑质移植所补偿。在其中两只动物中，将辣根过氧化物酶-小麦胚凝集素复合物注入移植体，以追踪来自宿主纹状体至移植体可能的相互传入连接。可见来自移植体的TH免疫反应性轴突与宿主新纹状体中的神经元成分形成大量对称突触。这些突触中85%至90%位于树突干和棘上，其余位于神经元胞体上。确定了两个主要靶点：棘状神经元的树突，其中大多数可能是纹状体投射神经元；以及大神经元的胞体，已知其中大多数（或可能全部）是胆碱能中间神经元。移植体中TH阳性神经元形成的所有TH阳性突触中约40%形成于树突棘上，这些突触与正常动物中的突触相似，既与棘颈接触，又总是与一个接触棘头的不对称TH阴性突触相关联。大细胞胞体的神经支配约占所发现的所有TH阳性突触的6%，其显著异常之处在于，移植体来源的TH阳性纤维在大细胞体周围选择性地形成密集的细胞周“篮状”结构。这种结构在正常纹状体中从未见过，在移植动物的完整对侧纹状体中也未出现。有人提出，移植体这种明显的多巴胺能超神经支配可对再支配的宿主纹状体中的胆碱能中间神经元产生强大抑制作用，并且这种抑制机制可通过增强终止于棘状传出神经元上的DA突触的功能效应来辅助移植诱导的功能恢复。因此，这种双重神经支配可能有助于解释为什么移植体仅恢复一小部分纹状体DA神经支配就足以诱导例如损伤大鼠运动不对称的完全补偿。（摘要截短于400字）
