Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice
Reduced expression of the vesicular acetylcholine transporter causes learning deficits in mice
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DOI：
10.1111/j.1601-183x.2008.00439.x
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发表时间：
2009-02-01
影响因子：
2.5
通讯作者：
Prado, M. A. M.
中科院分区：
文献类型：
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作者：
de Castro, B. M.;Pereira, G. S.;Prado, M. A. M.
突触囊泡中乙酰胆碱的储存在维持胆碱能功能方面发挥着关键作用。在这里，我们使用的小鼠与靶向突变的囊泡乙酰胆碱转运蛋白（VAChT）基因，减少转运蛋白表达的40%，调查认知加工条件下VAChT缺陷。在旋转棒中的运动技能学习表明，VAChT突变小鼠学习这项任务的速度较慢，但一旦它们达到最大性能，它们与野生型小鼠没有区别。有趣的是，这些突变小鼠在10天后的运动技能表现维持不受影响。我们还测试了是否减少VAChT水平影响学习的对象识别记忆任务。我们发现，VAChT突变小鼠提出了一个赤字的时间顺序版本的物体识别记忆所需的记忆编码，但没有改变空间工作记忆，或空间记忆一般测试时，在Morris水迷宫测试。在VAChT突变小鼠中观察到的物体识别记忆中的记忆缺陷可以通过胆碱酯酶抑制剂逆转，这表明由VAChT表达减少引起的学习缺陷可以通过恢复突触中的ACh水平来改善。这些数据表明，胆碱能紧张在运动学习和物体识别记忆中的重要作用。
Storage of acetylcholine in synaptic vesicles plays a key role in maintaining cholinergic function. Here we used mice with a targeted mutation in the vesicular acetylcholine transporter (VAChT) gene that reduces transporter expression by 40% to investigate cognitive processing under conditions of VAChT deficiency. Motor skill learning in the rotarod revealed that VAChT mutant mice were slower to learn this task, but once they reached maximum performance they were indistinguishable from wild-type mice. Interestingly, motor skill performance maintenance after 10 days was unaffected in these mutant mice. We also tested whether reduced VAChT levels affected learning in an object recognition memory task. We found that VAChT mutant mice presented a deficit in memory encoding necessary for the temporal order version of the object recognition memory, but showed no alteration in spatial working memory, or spatial memory in general when tested in the Morris water maze test. The memory deficit in object recognition memory observed in VAChT mutant mice could be reversed by cholinesterase inhibitors, suggesting that learning deficits caused by reduced VAChT expression can be ameliorated by restoring ACh levels in the synapse. These data indicate an important role for cholinergic tone in motor learning and object recognition memory.