Precise localization of α7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area
Precise localization of α7 nicotinic acetylcholine receptors on glutamatergic axon terminals in the rat ventral tegmental area
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DOI：
10.1523/jneurosci.3009-04.2004
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发表时间：
2004-12-15
影响因子：
5.3
通讯作者：
Wonnacott, S
中科院分区：
文献类型：
--
作者：
Jones, IW;Wonnacott, S
α 7神经元烟碱乙酰胆碱受体（nAChR）构成哺乳动物脑中主要的nAChR亚型之一。在腹侧被盖区（VTA）内，尼古丁应用与突触后刺激相结合，有助于形成一种形式的长时程增强，这是一种归因于突触前α 7 nAChR对多巴胺能传入的影响（Mansvelder和麦基希，2000）。本研究的目的是研究在成年大鼠腹侧被盖区的α 7 nAChRs的精确亚细胞分布，以确定这些受体是否确实存在于神经元轴突终末，并确定它们与胆碱能传入的关系。α 7乙酰胆碱受体，标记使用α 7乙酰胆碱受体特异性拮抗剂α-银环蛇毒素，和当地的神经化学环境之间的空间关系进行了研究，通过应用多种标记策略与抗体对酪氨酸羟化酶，囊泡谷氨酸转运蛋白（VGluTs），囊泡乙酰胆碱转运蛋白，和胶质细胞酸性蛋白。α 7 nAChR定位于腹侧被盖区内的体树突和突触前位点：多巴胺能和非多巴胺能神经元亚群以及多巴胺能和非谷氨酸能终末。在腹侧被盖区的星形胶质细胞内没有可检测到的α 7 nAChR表达。大多数α 7 nAChR是细胞质的（82%），其余的与质膜相关。大多数突触前受体（75%）的神经元轴突终端，与类似水平的α-银环蛇毒素结合存在于VGluT 1和VGluT 2的免疫反应终扣。嵌入前和嵌入后的电子显微镜显示，突触前α 7 nAChRs通常位于突触外（27%）和突触周围（61%）的位点。α 7 nAChR与胆碱能突触无关，这与它们通过乙酰胆碱或胆碱传递的旁分泌模式激活一致。
alpha7 neuronal nicotinic acetylcholine receptors (nAChRs) constitute one of the predominant nAChR subtypes in the mammalian brain. Within the ventral tegmental area (VTA), nicotine application, paired with postsynaptic stimulation, contributes to a form of long-term potentiation, an effect attributed to presynaptic alpha7 nAChRs on glutamatergic afferents (Mansvelder and McGehee, 2000). The aim of this study was to examine the precise subcellular distribution of alpha7 nAChRs in the adult rat VTA to establish whether these receptors are indeed present on glutamatergic axon terminals and to determine their relationship with cholinergic afferents. The spatial relationship between alpha7 nAChRs, labeled using the alpha7 nAChR-specific antagonist alpha-bungarotoxin, and the local neurochemical environment was investigated by the application of multiple labeling strategies with antibodies against tyrosine hydroxylase, vesicular glutamate transporters (VGluTs), vesicular acetylcholine transporter, and glial fibrillary acidic protein. alpha7 nAChRs were localized at both somatodendritic and presynaptic loci within the VTA: on subpopulations of dopaminergic and nondopaminergic neurons and glutamatergic and nonglutamatergic terminals. There was no detectable alpha7 nAChR expression within astrocytes in the VTA. Most alpha7 nAChRs were cytoplasmic (82%), and the remainder were associated with the plasma membrane. Most presynaptic receptors (75%) were on glutamatergic axon terminals, with similar levels of alpha-bungarotoxin binding present on both VGluT1-and VGluT2-immunoreactive boutons. Both preembedding and postembedding electron microscopy revealed that presynaptic alpha7 nAChRs are often located at extrasynaptic (27%) and perisynaptic (61%) loci. alpha7 nAChRs were not associated with cholinergic synapses, consistent with their activation by a paracrine mode of acetylcholine or choline delivery.