Gracy K N, Pickel V M
Department of Neurology and Neuroscience, Cornell University Medical College, New York, NY 10021, USA.
Brain Res. 1996 Nov 11;739(1-2):169-81. doi: 10.1016/s0006-8993(96)00822-0.
The N-methyl-D-aspartate (NMDA)-type glutamate receptors in the shell region of the nucleus accumbens (ACB) have been implicated in the modulation of dopamine release and in amphetamine-induced neurotoxicity. We used electron microscopic immunocyto-chemistry to determine the anatomical sites for NMDA-mediated effects of glutamate and for their potential interactions with dopaminergic afferents identified by the presence of tyrosine hydroxylase (TH) in this region of the rat brain. Immunogold and immunoperoxidase methods were used to localize antisera against the R1 subunit of the NMDA receptor (NMDAR1) alone or combined with TH. In single labeling experiments, approximately half of the NMDAR1-like immunoreactivity (NMDAR1-LI) was localized to extrasynaptic plasma membranes of neuronal processes, many (92 out of 215) of which were dendrites, and only 33 out of 215 were unmyelinated axons or terminals. Surprisingly, the neuronal labeling of NMDAR1 was almost equaled by that seen in astrocytic processes (88 out of 215). Dual labeling for TH and NMDAR1 was rarely observed and was only seen in axons. However, in favorable planes of section, NMDAR1 was noted along intervaricose segments of axons in which TH was more readily seen in the varicosity. This differential intra-axonal distribution suggests an underestimation of dual labeling in single coronal sections through unmyelinated axons and terminals. The TH-immunoreactive terminals were more often seen apposed to NMDA-immunoreactive astrocytic processes and dendrites. These results provide the first ultrastructural evidence for presynaptic modulation of dopamine release by NMDA receptors in the shell of the nucleus accumbens. They also indicate that NMDA receptors modulate postsynaptic neurons receiving input from the dopaminergic afferents and suggest a previously unsuspected functional association involving glial NMDA receptors and dopaminergic afferents in this brain region.
伏隔核（ACB）壳区的N-甲基-D-天冬氨酸（NMDA）型谷氨酸受体与多巴胺释放的调节以及苯丙胺诱导的神经毒性有关。我们使用电子显微镜免疫细胞化学方法来确定谷氨酸NMDA介导作用的解剖学部位，以及它们与该大鼠脑区中由酪氨酸羟化酶（TH）确定的多巴胺能传入神经之间潜在的相互作用。免疫金法和免疫过氧化物酶法用于单独定位针对NMDA受体（NMDAR1）R1亚基的抗血清，或与TH联合定位。在单标记实验中，约一半的NMDAR1样免疫反应性（NMDAR1-LI）定位于神经突的突触外质膜，其中许多（215个中有92个）是树突，而215个中只有33个是无髓轴突或终末。令人惊讶的是，NMDAR1在神经元中的标记几乎与在星形胶质细胞突起中所见的标记相当（215个中有88个）。很少观察到TH和NMDAR1的双重标记，仅在轴突中可见。然而，在有利的切片平面中，可以看到NMDAR1沿着轴突的曲张段分布，并在曲张体中更容易看到TH。这种轴突内的差异分布表明，通过无髓轴突和终末的单冠状切片可能低估了双重标记。TH免疫反应性终末更常与NMDA免疫反应性星形胶质细胞突起和树突相邻。这些结果为伏隔核壳区中NMDA受体对多巴胺释放的突触前调节提供了首个超微结构证据。它们还表明，NMDA受体调节接受多巴胺能传入神经输入的突触后神经元，并提示在该脑区中涉及胶质细胞NMDA受体和多巴胺能传入神经的一种先前未被怀疑的功能关联。
