Expression of mu opioid receptor in dorsal diencephalic conduction system: new insights for the medial habenula.

Expression of mu opioid receptor in dorsal diencephalic conduction system: new insights for the medial habenula.
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DOI:
10.1016/j.neuroscience.2014.07.053
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发表时间:
2014-09-26
期刊:
影响因子:
3.3
通讯作者:
Kieffer, B. L.
Kieffer, B. L.
中科院分区:
医学3区
文献类型:
--
作者:
Gardon, O.;Faget, L.;Chung, P. Chu Sin;Matifas, A.;Massotte, D.;Kieffer, B. L.

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缰状复合体,包括内侧分裂(MHb)和外侧分裂(LHb),是一个高度保守的上皮结构,参与间脑背传导系统(DDC)。这些脑核调节边缘前脑与中脑和后脑之间的信息流,整合认知、情感和感觉过程。MHb也是阿片受体(MORs)的最强表达位点之一,MORs介导阿片的镇痛和奖励特性。然而,目前对这些受体在MHb通路中的解剖分布和功能研究甚少。在这里,我们利用新生成的MOR-mcherry敲入小鼠系来表征DDC中的MOR表达位点。MOR-mcherry荧光信号在外侧束中较弱,而在内侧束、后屈束和束间核(IPN)中有较强的表达,表明MOR主要存在于MHb-IPN通路。在MHb的基底外侧和顶端都检测到mori -mcherry细胞体,其中受体分别与胆碱能和P物质(SP)神经元共定位,代表两种主要的MHb神经元群体。mcherry在大多数MHb-SP神经元中表达,仅存在于mhb -胆碱能神经元的一个亚群中。在IPN的侧部和吻部检测到强烈的漫射荧光,进一步表明mori -mcherry被运输到这些SP和胆碱能神经元的末端。最后,mir -mcherry存在于向MHb投射的间隔区,以及中央和中间IPN的神经元中。总之,这项研究描述了MOR在MHb-IPN电路的几个隔室中的表达。MHb-IPN通路中异常高的MOR密度表明,这些受体在介导镇痛、自主神经和奖励反应方面处于独特的地位。
The habenular complex, encompassing medial (MHb) and lateral (LHb) divisions, is a highly conserved epithalamic structure involved in the dorsal diencephalic conduction system (DDC). These brain nuclei regulate information flow between the limbic forebrain and the mid- and hindbrain, integrating cognitive with emotional and sensory processes. The MHb is also one of the strongest expression sites for mu opioid receptors (MORs), which mediate analgesic and rewarding properties of opiates. At present however, anatomical distribution and function of these receptors have been poorly studied in MHb pathways. Here we took advantage of a newly generated MOR-mcherry knock-in mouse line to characterize MOR expression sites in the DDC. MOR-mcherry fluorescent signal is weak in the lateral habenula, but strong expression is visible in the medial habenula, fasciculus retroflexus and interpeduncular nucleus (IPN), indicating that MOR is mainly present in the MHb-IPN pathway. MOR-mcherry cell bodies are detected both in basolateral and apical parts of MHb, where the receptor co-localizes with cholinergic and Substance P (SP) neurons, respectively, representing two main MHb neuronal populations. MOR-mcherry is expressed in most MHb-SP neurons, and is present in only a subpopulation of MHb-cholinergic neurons. Intense diffuse fluorescence detected in lateral and rostral parts of the IPN further suggests that MOR-mcherry is transported to terminals of these SP and cholinergic neurons. Finally, MOR-mcherry is present in septal regions projecting to the MHb, and in neurons of the central and intermediate IPN. Together, this study describes MOR expression in several compartments of the MHb-IPN circuitry. The remarkably high MOR density in the MHb-IPN pathway suggests that these receptors are in a unique position to mediate analgesic, autonomic and reward responses.
缰核:脊椎动物大脑中保守的不对称中继站。
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