Mu-opioid and corticotropin-releasing-factor receptors show largely postsynaptic co-expression, and separate presynaptic distributions, in the mouse central amygdala and bed nucleus of the stria terminalis.

Mu-opioid and corticotropin-releasing-factor receptors show largely postsynaptic co-expression, and separate presynaptic distributions, in the mouse central amygdala and bed nucleus of the stria terminalis.
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DOI:
10.1016/j.neuroscience.2008.12.061
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发表时间:
2009-03-17
期刊:
影响因子:
3.3
通讯作者:
Pickel, V. M.
Pickel, V. M.
中科院分区:
医学3区
文献类型:
--
作者:
Jaferi, A.;Pickel, V. M.

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阿片类药物对μ-阿片受体(μ-OR)的抗焦虑作用可能部分归因于抑制中央杏仁核(CeA)和终纹床核(BNST)中对应激相关肽促肾上腺皮质激素释放因子(CRF)有反应的神经元。CRF受体(CRFr)和μ-OR在CeA和BNST中均表达,但它们在两个区域中的亚细胞关系尚不清楚。为了解决这个问题,我们在小鼠外侧CeA和前外侧BNST中使用μ-OR和CRFr的双重电子显微镜免疫标记。免疫标记的每个受体中检测到的相同,以及在单独的体细胞,树突和轴突在每个区域的神经元的配置文件。CRFr在许多树突中具有质膜或胞质分布,包括共表达μ-OR的树突。CRFr和μ-OR的共表达也出现在树棘上的兴奋型突触附近。在CeA和BNST中,超过50%的CRFr标记的树突轮廓(树突和棘)含有μ-OR的免疫反应性。然而,不到25%的含有μ-OR的树突状轮廓在任一区域被标记为CRFr,这表明除了对CRF有反应的神经元之外,μ-OR的阿片激活还影响许多神经元。含有CRFr和/或μ-OR的树突轮廓接受来自未标记或CRFr标记的轴突终末的不对称的兴奋型突触。相反,μ-OR在形成对称的突触的终末中被鉴定。因此,在CeA和BNST中,μ-OR和CRFr具有调节CRF和阿片对单个神经元突触后兴奋性以及兴奋性和抑制性神经递质各自的突触前释放的作用的战略位置。CeA和BNST中两种受体的突触位置的共性表明这是与药物成瘾和应激诱导的疾病相关的基本细胞关联。
The anxiolytic effects of opiates active at the mu-opioid receptor (μ-OR) may be ascribed, in part, to suppression of neurons that are responsive to the stress-associated peptide, corticotropin releasing factor (CRF), in the central amygdala (CeA) and bed nucleus of the stria terminalis (BNST). The CRF receptor (CRFr) and μ-OR are expressed in both the CeA and BNST, but their subcellular relationship to each other is not known in either region. To address this question, we used dual electron microscopic immunolabeling of μ-OR and CRFr in the mouse lateral CeA and anterolateral BNST. Immunolabeling for each receptor was detected in the same as well as in separate somatic, dendritic and axonal profiles of neurons in each region. CRFr had a plasmalemmal or cytoplasmic distribution in many dendrites, including those co-expressing μ-OR. The co-expression of CRFr and μ-OR also was seen near excitatory-type synapses on dendritic spines. In both the CeA and BNST, over 50% of the CRFr-labeled dendritic profiles (dendrites and spines) contained immunoreactivity for the μ-OR. However, less than 25% of the dendritic profiles containing the μ-OR were labeled for CRFr in either region, suggesting that opiate activation of the μ-OR affects many neurons in addition to those responsive to CRF. The dendritic profiles containing CRFr and/or μ-OR received asymmetric, excitatory-type synapses from unlabeled or CRFr-labeled axon terminals. In contrast, the μ-OR was identified in terminals forming symmetric, inhibitory-type synapses. Thus, in both the CeA and BNST, μ-OR and CRFr have strategic locations for mediation of CRF and opioid effects on the postsynaptic excitability of single neurons, and on the respective presynaptic release of excitatory and inhibitory neurotransmitters. The commonalities in the synaptic location of both receptors in the CeA and BNST suggest that this is a fundamental cellular association of relevance to both drug addiction and stress-induced disorders.
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