Spatial and intracellular relationships between the alpha7 nicotinic acetylcholine receptor and the vesicular acetylcholine transporter in the prefrontal cortex of rat and mouse.
Spatial and intracellular relationships between the alpha7 nicotinic acetylcholine receptor and the vesicular acetylcholine transporter in the prefrontal cortex of rat and mouse.
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DOI：
10.1016/j.neuroscience.2009.04.024
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发表时间：
2009-07-21
期刊：
影响因子：
3.3
通讯作者：
Pickel, V. M.
中科院分区：
文献类型：
--
作者：
Duffy, A. M.;Zhou, P.;Milner, T. A.;Pickel, V. M.
烟碱乙酰胆碱受体（α 7 nAChR）的α-7亚基在前额叶皮层（PFC）中表达，这是一个脑区，这些受体与认知功能和精神分裂症的病理生理学有关。这种受体的激活依赖于从含有囊泡乙酰胆碱转运体（VAChT）的轴突末端释放乙酰胆碱（ACh）。由于大鼠和小鼠模型被广泛用于精神分裂症特定异常的研究，我们试图确定α 7 nAChR相对于VAChT储存囊泡在两个物种PFC轴突终末的亚细胞位置。为此，我们使用双电子显微镜免疫金和免疫过氧化物酶标记的抗血清提出的α 7 nAChR和VAChT。在两种动物中，α 7 nAChR免疫反应（-ir）主要在树突和树突棘内，可与轴突终末形成非对称兴奋型突触，但缺乏可检测到的α 7 nAChR或VAChT-ir。65%（299/463）为突触后结构（树突和树突棘），只有22%（104/463）为轴突终末或小的无髓轴突。与此相反，VAChT主要定位于静脉曲张囊泡填充的轴突配置文件，没有公认的突触专业化（n = 240）。在α 7 nAChR标记的轴突中，47%（37/79）也含有VAChT，表明ACh的释放是通过突触前α 7 nAChR自身调节的。VAChT标记的终末很少形成突触，但经常与含α 7 nAChR的神经元轮廓并置。这些结果表明，在啮齿类PFC中，α 7 nAChR在调节与含有VAChT的轴突接触的棘状树突的突触后兴奋中起主要作用。
The alpha-7 subunit of the nicotinic acetylcholine receptor (α7nAChR) is expressed in the prefrontal cortex (PFC), a brain region where these receptors are implicated in cognitive function and in the pathophysiology of schizophrenia. Activation of this receptor is dependent on release of acetylcholine (ACh) from axon terminals that contain the vesicular acetylcholine transporter (VAChT). Since rat and mouse models are widely used for studies of specific abnormalities in schizophrenia, we sought to determine the subcellular location of the α7nAChR with respect to VAChT storage vesicles in axon terminals in the PFC in both species. For this, we used dual electron microscopic immunogold and immunoperoxidase labeling of antisera raised against the α7nAChR and VAChT. In both species, the α7nAChR-immunoreactivity (-ir) was principally identified within dendrites and dendritic spines, receptive to axon terminals forming asymmetric excitatory-type synapses, but lacking detectable α7nAChR or VAChT-ir. Quantitative analysis of the rat PFC revealed that of α7nAChR labeled neuronal profiles, 65% (299/463) were postsynaptic structures (dendrites and dendritic spine) and only 22% (104/463) were axon terminals or small unmyelinated axons. In contrast, VAChT was principally localized to varicose vesicle-filled axonal profiles, without recognized synaptic specializations (n = 240). Of the α7nAChR-labeled axons, 47% (37/79) also contained VAChT, suggesting that ACh release is autoregulated through the presynaptic α7nAChR. The VAChT-labeled terminals rarely formed synapses, but frequently apposed α7nAChR-containing neuronal profiles. These results suggest that in rodent PFC, the α7nAChR plays a major role in modulation of the postsynaptic excitation in spiny dendrites in contact with VAChT containing axons.
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影响因子：
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