Ultrastructural relationship between the AMPA-GluR2 receptor subunit and the mu-opioid receptor in the mouse central nucleus of the amygdala.

Ultrastructural relationship between the AMPA-GluR2 receptor subunit and the mu-opioid receptor in the mouse central nucleus of the amygdala.
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DOI:
10.1016/j.expneurol.2010.10.010
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发表时间:
2011-01
影响因子:
5.3
通讯作者:
Glass, Michael J.
Glass, Michael J.
中科院分区:
医学2区
文献类型:
--
作者:
Beckerman, Marc A.;Glass, Michael J.

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杏仁中央核(CEA)表达非钙通透性AMPA型谷氨酸受体的GluR2的激活可能在阿片成瘾相关的情绪和记忆与目标导向行为的整合中发挥重要作用。非钙通透性AMPA受体位于不同的神经元区段(即胞体、树突或轴突)是这些蛋白的一个重要功能特征,但它们在CEA中的超微结构定位及其与单位阿片受体(μOR)的亚细胞关系尚不清楚。免疫细胞化学电子显微镜观察GluR2超微结构在小鼠癌胚抗原中的分布及其与μOR的关系。用免疫过氧化物酶或免疫金标记物对GluR2分布的单一标记分析表明,该蛋白经常附属于细胞内的囊泡细胞器以及CEA神经元轮廓的质膜。在所有GluR2标记的神经元结构中,85%以上是树突或胞体。未标记的轴突终末经常与GluR2标记的树突状突触形成不对称的兴奋性突触连接。免疫细胞化学双标记法显示,Glu R2和μOR共定位于神经元室。在所有的双标记结构中,大约80%是树突。这些双标记树突的突触输入通常来自形成不对称兴奋性突触的未标记轴突终末。GluR2在接受不对称突触的树突状结构中的存在表明,非钙通透性AMPA受体的激活在兴奋性信号的突触后调制中发挥作用,涉及CEA神经元回路,协调与药物成瘾有关的感觉、情感和行为过程。鉴于非钙通透性AMPA受体功能在神经和行为适应中的关键作用,它们与μ或CEA树突中的树突状联系为阿片介导的可塑性提供了神经元底物。
Activation of GluR2 expressing non-calcium permeable AMPA-type glutamate receptors in the central nucleus of the amygdala (CeA) may play an important role in integrating emotion and memory with goal directed behaviors involved in opioid addiction. The location of non-calcium permeable AMPA receptors within distinct neuronal compartments (i.e. soma, dendrite, or axon) is an important functional feature of these proteins, however, their ultrastructural location and subcellular relationship with mu-opioid receptors (μOR) in the CeA are unknown. Immunocytochemical electron microscopy was used to characterize the ultrastructural distribution of GluR2 and its association with μOR in the mouse CeA. A single labeling analysis of GluR2 distribution employing immunoperoxidase or immunogold markers revealed that this protein was frequently affiliated with intracellular vesicular organelles, as well as the plasma membrane of CeA neuronal profiles. Among all GluR2 labeled neuronal structures, over 85% were dendrites or somata. Unlabeled axon terminals frequently formed asymmetric excitatory-type synaptic junctions with GluR2 labeled dendritic profiles. Dual labeling immunocytochemical analysis showed that GluR2 and μOR were co-localized in neuronal compartments. Among all dual labeled structures, approximately 80% were dendritic. Synaptic inputs to these dual labeled dendrites were frequently from unlabeled axon terminals forming asymmetric excitatory-type synapses. The presence of GluR2 in dendritic profiles receiving asymmetric synapses suggests that activation of the non-calcium permeable AMPA receptor plays a role in the postsynaptic modulation of excitatory signaling involving CeA neuronal circuits that coordinate sensory, affective, and behavioral processes involved in drug addiction. Given the critical role of non-calcium permeable AMPA receptor function in neural and behavioral adaptability, their dendritic association with μOR in CeA dendrites provides a neuronal substrate for opioid-mediated plasticity.
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DOI: 10.1016/s0083-6729(10)82008-4
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作者:
Glass MJ
通讯作者: Glass MJ