Enhancement in motor learning through genetic manipulation of the Lynx1 gene.
Enhancement in motor learning through genetic manipulation of the Lynx1 gene.
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DOI：
10.1371/journal.pone.0043302
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Walz A
中科院分区：
文献类型：
--
作者：
Miwa JM;Walz A
胆碱能系统是一种神经调节神经递质系统，涉及多种大脑过程，包括学习和记忆，注意力和运动过程等。烟碱乙酰胆碱受体对胆碱能系统的影响由山猫蛋白调节，山猫蛋白是一种与烟碱受体紧密结合的gpi锚定膜蛋白。先前的研究表明，lynx1抑制尼古丁受体功能并限制神经元的可塑性。我们试图研究lynx1对尼古丁受体功能的作用机制，通过生成表达可溶性lynx1的山猫小鼠模型，并将结果与全长过表达进行比较。使用rotarod作为运动学习测试，我们发现表达lynx的分泌变体导致运动学习增强，而过表达全长lynx则没有效果。此外，成年lynx1KO小鼠表现出与可溶性转基因系相当的运动学习增强，而以前，老年lynx1KO小鼠仅在尼古丁治疗下表现出性能增强。由此我们得出结论，运动学习对山猫功能的丧失更为敏感，GPI锚点在山猫蛋白的正常功能中起作用。此外，我们的数据表明，山猫基因在大脑衰老过程中起调节作用，并且山猫的可溶性版本有可能作为调节大脑中胆碱能依赖的可塑性和学习机制的工具。
The cholinergic system is a neuromodulatory neurotransmitter system involved in a variety of brain processes, including learning and memory, attention, and motor processes, among others. The influence of nicotinic acetylcholine receptors of the cholinergic system are moderated by lynx proteins, which are GPI-anchored membrane proteins forming tight associations with nicotinic receptors. Previous studies indicate lynx1 inhibits nicotinic receptor function and limits neuronal plasticity. We sought to investigate the mechanism of action of lynx1 on nicotinic receptor function, through the generation of lynx mouse models, expressing a soluble version of lynx and comparing results to the full length overexpression. Using rotarod as a test for motor learning, we found that expressing a secreted variant of lynx leads to motor learning enhancements whereas overexpression of full-length lynx had no effect. Further, adult lynx1KO mice demonstrated comparable motor learning enhancements as the soluble transgenic lines, whereas previously, aged lynx1KO mice showed performance augmentation only with nicotine treatment. From this we conclude the motor learning is more sensitive to loss of lynx function, and that the GPI anchor plays a role in the normal function of the lynx protein. In addition, our data suggests that the lynx gene plays a modulatory role in the brain during aging, and that a soluble version of lynx has potential as a tool for adjusting cholinergic-dependent plasticity and learning mechanisms in the brain.