Milner T A, Drake C T
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY 10021, USA.
Brain Res Bull. 2001 Jan 15;54(2):131-40. doi: 10.1016/s0361-9230(00)00415-9.
Physiological studies have demonstrated that long-term potentiation (LTP) induction in N-methyl-D-aspartate (NMDA) receptor containing dentate granule cells following lateral perforant path stimulation is opioid dependent, involving mu-opioid receptors (MORs) on gamma-aminobutyric acid (GABA)-ergic neurons. To determine the cellular relationships of MORs to postsynaptic NMDA receptor-containing dendrites, immunoreactivity (-I) against MOR and the NMDA receptor subunit 1 (NMDAR1) was examined in the outer molecular layer of the dentate gyrus using electron microscopy. MOR-I was predominantly in axons and axon terminals. NMDAR1-I was almost exclusively in spiny dendrites, but was also in a few terminals. Using immunogold particles to localize precisely NMDAR1, one-third of the NMDAR1-I was detected on the dendritic plasmalemma; in dendritic spines plasmalemmal immunogold particles were near synaptic densities. Many MOR-labeled axons and terminals contacted NMDAR1-labeled dendrites. MOR-labeled terminals formed symmetric (inhibitory-type) synapses on NMDAR1-labeled dendritic shafts or nonsynaptically contacted NMDAR1-labeled shafts and spines. MOR-labeled axons often abutted NMDAR1-containing dendritic spines which received asymmetric (excitatory-type) synapses from unlabeled terminals. Occasionally, MOR-labeled terminals and dendrites were apposed to NMDAR1-containing terminals. These results provide anatomical evidence that endogenous enkephalins or exogenous opioid agonists could inhibit GABAergic terminals that modulate granule cell dendrites, thus boosting depolarizing events in granule cells and facilitating the activation of NMDA receptors located on their dendrites.
生理学研究表明，在外侧穿通路径刺激后，含N-甲基-D-天冬氨酸（NMDA）受体的齿状颗粒细胞中的长时程增强（LTP）诱导是阿片类药物依赖性的，涉及γ-氨基丁酸（GABA）能神经元上的μ-阿片受体（MORs）。为了确定MORs与含NMDA受体的突触后树突的细胞关系，使用电子显微镜在齿状回的外分子层中检测了针对MOR和NMDA受体亚基1（NMDAR1）的免疫反应性（-I）。MOR-I主要存在于轴突和轴突终末。NMDAR1-I几乎只存在于棘状树突中，但也存在于少数终末中。使用免疫金颗粒精确地定位NMDAR1，在树突质膜上检测到三分之一的NMDAR1-I；在树突棘中，质膜免疫金颗粒靠近突触致密物。许多标记有MOR的轴突和终末与标记有NMDAR1的树突接触。标记有MOR的终末在标记有NMDAR1的树突干上形成对称（抑制型）突触，或与标记有NMDAR1的树突干和棘进行非突触接触。标记有MOR的轴突常常邻接含有NMDAR1的树突棘，这些树突棘接受来自未标记终末的不对称（兴奋型）突触。偶尔，标记有MOR的终末和树突与含有NMDAR1的终末并列。这些结果提供了解剖学证据，表明内源性脑啡肽或外源性阿片类激动剂可以抑制调节颗粒细胞树突功能的GABA能终末，从而增强颗粒细胞中的去极化事件，并促进位于其树突上的NMDA受体的激活。
