Phenotypic characterization of an α4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse
Phenotypic characterization of an α4 neuronal nicotinic acetylcholine receptor subunit knock-out mouse
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DOI：
10.1523/jneurosci.20-17-06431.2000
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发表时间：
2000-09-01
影响因子：
5.3
通讯作者：
Drago, J
中科院分区：
文献类型：
--
作者：
Ross, SA;Wong, JYF;Drago, J
神经元烟碱乙酰胆碱受体（nAChR）以高丰度存在于神经系统中（德克尔等人，1995年）。在脑中有大量的亚基表达，它们联合收割机形成多聚体功能受体。我们已经产生了α（4）nAChR亚基敲除线，并专注于定义该受体亚基的行为作用。纯合子突变小鼠（Mt）在大小、生育力和笼内行为方面正常。自发的无条件运动行为显示的行为特征显着增加的几个地形的探索行为在MT相对于野生型小鼠（Wt）的过程中习惯于一个新的环境。此外，在高架十字迷宫试验中，MT的行为与焦虑的基础水平增加一致。在尼古丁的反应中，Wt在非习惯和习惯条件下表现出许多行为地形图的早期减少;相反，在非习惯条件的后期阶段，尼古丁降低了Mt中行为地形图的水平。配体放射自显影证实缺乏高亲和力结合放射性标记的尼古丁，野靛碱，和epibatidine在丘脑，皮质和尾壳核，虽然结合到一些离散的核仍然。这项研究证实了α（4）nAChR亚单位在调节正常小鼠行为图的许多成分和使用十字迷宫评估的焦虑中发挥的关键作用。此外，MT对尼古丁给药的反应表明，缰脚间系统中的持久尼古丁结合位点足以调节主动探索小鼠的运动活动。
Neuronal nicotinic acetylcholine receptors (nAChR) are present in high abundance in the nervous system (Decker et al., 1995). There are a large number of subunits expressed in the brain that combine to form multimeric functional receptors. We have generated an alpha(4) nAChR subunit knock-out line and focus on defining the behavioral role of this receptor subunit. Homozygous mutant mice (Mt) are normal in size, fertility, and home-cage behavior. Spontaneous unconditioned motor behavior revealed an ethogram characterized by significant increases in several topographies of exploratory behavior in Mt relative to wild-type mice (Wt) over the course of habituation to a novel environment. Furthermore, the behavior of Mt in the elevated plus-maze assay was consistent with increased basal levels of anxiety. In response to nicotine, Wt exhibited early reductions in a number of behavioral topographies, under both unhabituated and habituated conditions; conversely, heightened levels of behavioral topographies in Mt were reduced by nicotine in the late phase of the unhabituated condition. Ligand autoradiography confirmed the lack of high-affinity binding to radiolabeled nicotine, cytisine, and epibatidine in the thalamus, cortex, and caudate putamen, although binding to a number of discrete nuclei remained. The study confirms the pivotal role played by the alpha(4) nAChR subunit in the modulation of a number of constituents of the normal mouse ethogram and in anxiety as assessed using the plus-maze. Furthermore, the response of Mt to nicotine administration suggests that persistent nicotine binding sites in the habenulointerpeduncular system are sufficient to modulate motor activity in actively exploring mice.