Bolam J P, Freund T F, Björklund A, Dunnett S B, Smith A D
MRC Anatomical Neuropharmacology Unit, University Department of Pharmacology, Oxford, U.K.
Exp Brain Res. 1987;68(1):131-46. doi: 10.1007/BF00255240.
In adult rats with a unilateral 6-hydroxy-dopamine-induced lesion of the nigrostriatal dopamine pathway, grafts of embryonic ventral mesencephalon can establish extensive efferent connections with the previously denervated host neostriatum and can compensate for motor and sensorimotor asymmetries induced by the lesion. The object of this study was to examine the afferent synaptic inputs to grafted dopaminergic neurons, implanted into a cortical cavity overlying the previously denervated caudate-putamen, using electron microscopic immunocytochemistry. The dopaminergic neurons of the grafts in the same animals had previously been shown to re-innervate the host neostriatum, to form synaptic connections therein and to attenuate the lesion-induced motor asymmetry that occurred in response to amphetamine (Freund et al. 1985). In the light microscope, the grafts were found to contain numerous tyrosine hydroxylase-immunoreactive perikarya, dendrites, axons and axonal swellings which had distinct distributions. In addition axons and axonal swellings that were immunoreactive for either substance P or glutamate decarboxylase were present. Electron microscopic analysis of the boutons contacting tyrosine hydroxylase-immunoreactive neurons in the grafts revealed the presence of at least five distinct types of afferent synaptic boutons based on their immunochemistry, morphology, or types of membrane specialization. One type was itself immunoreactive for tyrosine hydroxylase; such synapses are extremely rare in the intact substantia nigra, none were found in the contralateral substantia nigrae or the substantia nigra of a control rat. Three of the remaining types had ultrastructural features that were similar to synaptic terminals that were immunoreactive for substance P or glutamate decarboxylase. These synapses were similar to the types of synapses found contacting dopaminergic neurons in the substantia nigra contralateral to the graft or the substantia nigra of a control rat. The results demonstrate that, in the absence of the normal extrinsic afferent inputs, the intracortical mesencephalic grafts have a well-developed local synaptic circuitry. It is suggested that local circuit regulation of dopaminergic neurons within the graft may, at least in part, be responsible for the maintenance of a normal or close to normal functional activity.
在单侧6-羟基多巴胺诱导黑质纹状体多巴胺能通路损伤的成年大鼠中，胚胎腹侧中脑移植体能与先前去神经支配的宿主新纹状体建立广泛的传出连接，并能补偿损伤所致的运动和感觉运动不对称。本研究的目的是利用电子显微镜免疫细胞化学技术，检测植入先前去神经支配的尾状核-壳核上方皮质腔内的移植多巴胺能神经元的传入突触输入。同一动物移植体中的多巴胺能神经元先前已被证明能重新支配宿主新纹状体，在其中形成突触连接，并减轻因苯丙胺引起的损伤诱导的运动不对称（弗罗因德等人，1985年）。在光学显微镜下，发现移植体含有大量酪氨酸羟化酶免疫反应阳性的胞体、树突、轴突和轴突膨体，它们具有不同的分布。此外，还存在对P物质或谷氨酸脱羧酶免疫反应阳性的轴突和轴突膨体。对移植体中与酪氨酸羟化酶免疫反应阳性神经元接触的终扣进行电子显微镜分析，根据其免疫化学、形态学或膜特化类型，发现至少存在五种不同类型的传入突触终扣。一种类型自身对酪氨酸羟化酶免疫反应阳性；这种突触在完整的黑质中极为罕见，在对侧黑质或对照大鼠的黑质中未发现。其余三种类型具有与对P物质或谷氨酸脱羧酶免疫反应阳性的突触终末相似的超微结构特征。这些突触与在移植对侧黑质或对照大鼠黑质中与多巴胺能神经元接触的突触类型相似。结果表明，在缺乏正常外在传入输入的情况下，皮质内中脑移植体具有发育良好的局部突触回路。提示移植体内多巴胺能神经元的局部回路调节可能至少部分负责维持正常或接近正常的功能活动。
