Smith Y, Charara A, Parent A
Centre de Recherche en Neurobiologie, Hôpital de l'Enfant-Jésus and Université Laval, Québec, Canada.
J Comp Neurol. 1996 Jan 8;364(2):231-53. doi: 10.1002/(SICI)1096-9861(19960108)364:2<231::AID-CNE4>3.0.CO;2-6.
The excitatory amino acid, glutamate, has long been thought to be a transmitter that plays a major role in the control of the firing pattern of midbrain dopaminergic neurons. The present study was aimed at elucidating the anatomical substrate that underlies the functional interaction between glutamatergic afferents and midbrain dopaminergic neurons in the squirrel monkey. To do this, we combined preembedding immunocytochemistry for tyrosine hydroxylase and calbindin D-28k with postembedding immunostaining for glutamate. On the basis of their ultrastructural features, three types (so-called types I, II, and III) of glutamate-enriched terminals were found to form asymmetric synapses with dendrites and perikarya of midbrain dopaminergic neurons. The type I terminals accounted for more than 70% of the total population of glutamate-enriched boutons in contact with dopaminergic cells in the dorsal and ventral tiers of the substantia nigra pars compacta as well as in the ventral tegmental area, whereas 5-20% of the glutamatergic synapses with dopaminergic neurons involved the two other types of terminals. The major finding of our study is that the glutamate-enriched boutons were involved in 70% of the axodendritic synapses in the ventral tegmental area. In contrast, less than 40% of the boutons in contact with dopaminergic dendrites were immunoreactive for glutamate in the dorsal and ventral tiers of the substantia nigra pars compacta. Approximately 50% of the terminals in contact with the perikarya of the different populations of midbrain dopaminergic neurons displayed glutamate immunoreactivity. In conclusion, our findings provide the first evidence that glutamate-enriched terminals form synapses with midbrain dopaminergic neurons in primates. The fact that the proportion of glutamatergic boutons in contact with dopaminergic cells is higher in the ventral tegmental area than in the substantia nigra pars compacta suggests that the different groups of midbrain dopaminergic neurons are modulated differently by extrinsic glutamatergic afferents in primates.
兴奋性氨基酸谷氨酸长期以来一直被认为是一种在控制中脑多巴胺能神经元放电模式中起主要作用的神经递质。本研究旨在阐明松鼠猴中谷氨酸能传入纤维与中脑多巴胺能神经元之间功能相互作用的解剖学基础。为此，我们将酪氨酸羟化酶和钙结合蛋白D - 28k的包埋前免疫细胞化学与谷氨酸的包埋后免疫染色相结合。根据其超微结构特征，发现三种富含谷氨酸的终末类型（即所谓的I型、II型和III型）与中脑多巴胺能神经元的树突和胞体形成不对称突触。I型终末在黑质致密部背侧和腹侧层以及腹侧被盖区与多巴胺能细胞接触的富含谷氨酸的终扣总数中占70%以上，而与多巴胺能神经元形成的谷氨酸能突触中，另外两种类型的终末占5 - 20%。我们研究的主要发现是，富含谷氨酸的终扣参与了腹侧被盖区70%的轴突 - 树突突触。相比之下，在黑质致密部背侧和腹侧层，与多巴胺能树突接触的终扣中，对谷氨酸呈免疫反应的不到40%。与不同群体的中脑多巴胺能神经元胞体接触的终末中，约50%显示谷氨酸免疫反应性。总之，我们的研究结果首次证明了富含谷氨酸的终末在灵长类动物中与中脑多巴胺能神经元形成突触。腹侧被盖区与多巴胺能细胞接触的谷氨酸能终扣比例高于黑质致密部，这一事实表明，在灵长类动物中，不同组的中脑多巴胺能神经元受到外在谷氨酸能传入纤维的调节方式不同。
