Department of Pathology and Cell Biology, Faculty of Medicine, C.P. 6128, Succursale Centre-Ville, Université de Montréal, Montréal, QC H3C 3J7, Canada.
Eur J Neurosci. 2012 Feb;35(4):527-38. doi: 10.1111/j.1460-9568.2012.07992.x.
Despite the increasing use of genetically modified mice to investigate the dopamine (DA) system, little is known about the ultrastructural features of the striatal DA innervation in the mouse. This issue is particularly relevant in view of recent evidence for expression of the vesicular glutamate transporter 2 (VGLUT2) by a subset of mesencephalic DA neurons in mouse as well as rat. We used immuno-electron microscopy to characterize tyrosine hydroxylase (TH)-labeled terminals in the core and shell of nucleus accumbens and the neostriatum of two mouse lines in which the Vglut2 gene was selectively disrupted in DA neurons (cKO), their control littermates, and C57BL/6/J wild-type mice, aged P15 or adult. The three regions were also examined in cKO mice and their controls of both ages after dual TH-VGLUT2 immunolabeling. Irrespective of the region, age and genotype, the TH-immunoreactive varicosities appeared similar in size, vesicular content, percentage with mitochondria, and exceedingly low frequency of synaptic membrane specialization. No dually labeled axon terminals were found at either age in control or in cKO mice. Unless TH and VGLUT2 are segregated in different axon terminals of the same neurons, these results favor the view that the glutamatergic cophenotype of mesencephalic DA neurons is more important during the early development of these neurons than for the establishment of their scarce synaptic connectivity. They also suggest that, in mouse even more than rat, the mesostriatal DA system operates mainly through non-targeted release of DA, diffuse transmission and the maintenance of an ambient DA level.
尽管越来越多地使用基因修饰小鼠来研究多巴胺（DA）系统，但对于小鼠纹状体 DA 支配的超微结构特征知之甚少。鉴于最近有证据表明，在小鼠和大鼠中，一部分中脑 DA 神经元表达囊泡谷氨酸转运体 2（VGLUT2），这一问题尤其重要。我们使用免疫电子显微镜来描述在核 accumbens 的核心和壳以及新纹状体中的酪氨酸羟化酶（TH）标记的终末，这两个小鼠品系中的 Vglut2 基因在 DA 神经元中被选择性破坏（cKO），其对照同窝仔和 C57BL/6/J 野生型小鼠，年龄为 P15 或成年。在 cKO 小鼠及其对照的两个年龄后，也对这三个区域进行了双重 TH-VGLUT2 免疫标记。无论区域、年龄和基因型如何，TH 免疫反应性的囊泡在大小、囊泡内容物、含有线粒体的百分比以及突触膜特化的极低频率方面似乎相似。在对照或 cKO 小鼠的任何年龄都没有发现双标记的轴突终末。除非 TH 和 VGLUT2 分别存在于同一神经元的不同轴突终末中，否则这些结果支持这样的观点，即中脑 DA 神经元的谷氨酸能表型在这些神经元的早期发育中比建立其稀少的突触连接更为重要。它们还表明，即使在小鼠中比在大鼠中，中脑纹状体 DA 系统主要通过 DA 的非靶向释放、弥散传递和维持环境 DA 水平来运作。
