Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition
Mice deficient for the vesicular acetylcholine transporter are myasthenic and have deficits in object and social recognition
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DOI：
10.1016/j.neuron.2006.08.005
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发表时间：
2006-09-07
期刊：
影响因子：
16.2
通讯作者：
Prado, Marco A. M.
中科院分区：
文献类型：
--
作者：
Prado, Vania F.;Martins-Silva, Cristina;Prado, Marco A. M.
胆碱能传递的一个重要步骤涉及乙酰胆碱（ACh）的囊泡储存，这一过程由囊泡乙酰胆碱转运蛋白（VAChT）介导。为了了解VAChT的生理作用，我们开发了一种基因改变的小鼠品系，这种转运蛋白的表达减少。杂合和纯合VAChT敲低小鼠的VAChT蛋白表达分别降低45%和65%。VAChT缺陷改变突触囊泡填充并影响ACh释放。而VAChT纯合子突变小鼠表现出主要的神经肌肉缺陷，VAChT杂合子小鼠在这方面表现正常，可用于分析中枢胆碱能功能。行为分析表明，变异小鼠的厌恶性学习和记忆没有改变，但是，在涉及对象和社会识别的认知任务中的表现严重受损。这些观察结果表明，VAChT在调节ACh的释放和生理功能的外周和中枢神经系统中的关键作用。
An important step for cholinergic transmission involves the vesicular storage of acetylcholine (ACh), a process mediated by the vesicular acetylcholine transporter (VAChT). In order to understand the physiological roles of the VAChT, we developed a genetically altered strain of mice with reduced expression of this transporter. Heterozygous and homozygous VAChT knockdown mice have a 45% and 65% decrease in VAChT protein expression, respectively. VAChT deficiency alters synaptic vesicle filling and affects ACh release. Whereas VAChT homozygous mutant mice demonstrate major neuromuscular deficits, VAChT heterozygous mice appear normal in that respect and could be used for analysis of central cholinergic function. Behavioral analyses revealed that aversive learning and memory are not altered in mutant mice; however, performance in cognitive tasks involving object and social recognition is severely impaired. These observations suggest a critical role of VAChT in the regulation of ACh release and physiological functions in the peripheral and central nervous system.