Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M2 muscarinic acetylcholine receptor subtype
Learning and memory impairments in a congenic C57BL/6 strain of mice that lacks the M2 muscarinic acetylcholine receptor subtype
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DOI：
10.1016/j.bbr.2008.02.001
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发表时间：
2008-06-26
影响因子：
2.7
通讯作者：
Wrenn, Craige C.
中科院分区：
文献类型：
--
作者：
Bainbridge, Natalie K.;Koselke, Lisa R.;Wrenn, Craige C.
神经递质乙酰胆碱是包括注意力、学习和记忆在内的认知功能的重要调节剂。乙酰胆碱的作用由五种不同的毒蕈碱乙酰胆碱受体亚型（M-1-M-5）介导。缺乏对这些亚型具有高度选择性的药物，阻碍了确定哪些亚型介导与认知能力相关的胆碱能神经传递的哪些组分。本研究利用具有M-2毒蕈碱受体基因零突变的同类C57 BL/6小鼠（M-2（-/-）小鼠）研究M-2毒蕈碱受体亚型的行为功能。对一般健康状况和神经功能的综合评估发现，M-2（-/-）和野生型（M-2（+/+））小鼠之间没有重大差异。在学习和记忆的测试中，M-2（-/-）小鼠在被动回避任务的获得（标准试验）中受损，但在保持（72 h）中未受损。在一个新的开放场地中，M-2（-/-）小鼠在训练期间的习惯性受损，但在训练期间的习惯性并未受损。在空间记忆的孔板测试中，M-2（-/-）小鼠比M-2（+/+）小鼠在工作记忆中犯更多的错误。参考记忆没有不同的基因型。M-2（-/-）小鼠在线索或情境恐惧条件反射中均未表现出损伤。这些发现复制并扩展了早期在杂交菌株中的发现，并巩固了M-2受体在认知能力的特定组成部分中起关键作用的解释。(c)2008 Elsevier B. V.保留所有权利。
The neurotransmitter acetylcholine is an important modulator of cognitive functions including attention, learning, and memory. The actions of acetylcholine are mediated by five distinct muscarinic acetylcholine receptor subtypes (M-1-M-5). The lack of drugs with a high degree of selectivity for these subtypes has impeded the determination of which subtypes mediate which components of cholinergic neurotransmission relevant to cognitive abilities. The present study examined the behavioral functions of the M-2 muscarinic receptor subtype by utilizing congenic C57BL/6 mice possessing a null-mutation in the M-2 muscarinic receptor gene (M-2(-/-) mice). Comprehensive assessment of general health and the neurological function found no major differences between M-2(-/-) and wild-type (M-2(+/+)) mice. In the tests of learning and memory, M-2(-/-) mice were impaired in the acquisition (trials to criterion), but not the retention (72 h) of a passive avoidance task. In a novel open field, M-2(-/-) mice were impaired in between-sessions, but not within-session habituation. In a holeboard test of spatial memory, M-2(-/-) mice committed more errors in working memory than M-2(+/+) mice. Reference memory did not differ between the genotypes. M-2(-/-) mice showed no impairments in either cued or contextual fear conditioning. These findings replicate and extend earlier findings in a hybrid strain and solidify the interpretation that the M-2 receptor plays a critical role in specific components of cognitive abilities. (c) 2008 Elsevier B.V. All rights reserved.