Liu H, Wang H, Sheng M, Jan L Y, Jan Y N, Basbaum A I
Department of Anatomy, University of California, San Francisco 94143.
Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8383-7. doi: 10.1073/pnas.91.18.8383.
The N-methyl-D-aspartate (NMDA) receptor has been implicated in a variety of systems that undergo plastic changes in the central nervous system. We used electron microscopic immunocytochemistry with an antibody directed against an alternatively spliced exon near the C terminus of NMDAR1, the essential functional subunit of the NMDA receptor, to study the distribution of the NMDA receptor in the spinal cord and CA1 region of the hippocampus, two regions where NMDA-mediated long-term plasticity has been demonstrated. In CA1, we found that the NMDA receptor is exclusively expressed on postsynaptic structures. By contrast, in the spinal cord we found that in about one-third of labeled synapses, the receptor is located in the presynaptic terminal, immediately adjacent to the vesicle release site at the active zone. Using combined postembedding immunocytochemistry, we also showed that > 70% of the NMDA receptor immunoreactive terminals are glutamate positive, which suggests that the presynaptic NMDA receptor is an autoreceptor. Nerve ligation studies demonstrated that the receptor is transported in dorsal roots and sciatic nerve to the spinal cord and periphery, respectively. These data indicate that an NMDA autoreceptor is located in terminals of primary afferent fibers, where it could facilitate the transmission of inputs to the spinal cord by increasing the release of neurotransmitter from the primary afferent terminal.
N-甲基-D-天冬氨酸（NMDA）受体与中枢神经系统中发生可塑性变化的多种系统有关。我们使用电子显微镜免疫细胞化学技术，用一种针对NMDA受体必需功能亚基NMDAR1 C末端附近一个可变剪接外显子的抗体，来研究NMDA受体在脊髓和海马体CA1区的分布，这两个区域已证实存在NMDA介导的长期可塑性。在CA1区，我们发现NMDA受体仅在突触后结构上表达。相比之下，在脊髓中我们发现，在约三分之一标记的突触中，该受体位于突触前终末，紧邻活性区的囊泡释放位点。通过联合包埋后免疫细胞化学技术，我们还表明超过70%的NMDA受体免疫反应性终末谷氨酸呈阳性，这表明突触前NMDA受体是一种自身受体。神经结扎研究表明，该受体分别通过背根和坐骨神经运输到脊髓和外周。这些数据表明，一种NMDA自身受体位于初级传入纤维的终末，在那里它可以通过增加初级传入终末神经递质的释放来促进向脊髓的输入传递。
