Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice
Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice
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DOI：
10.1038/nn992
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发表时间：
2003-01-01
影响因子：
25
通讯作者：
Silva, AJ
中科院分区：
文献类型：
--
作者：
Anagnostaras, SG;Murphy, GG;Silva, AJ
毒蕈碱受体拮抗剂阻断胆碱能神经传递会导致注意力和记忆力的严重缺陷。然而，在以前的研究中使用的拮抗剂结合到五种毒蕈碱受体亚型中的一种以上。在这里，我们研究了小鼠的记忆与无效突变的基因编码的M受体，最密集分布在海马和前脑的毒蕈碱受体。与以前使用非选择性药理学拮抗剂的研究相比，M-1受体缺失产生了一种选择性表型，包括记忆的增强和缺陷。在突变小鼠中，海马中对θ爆发刺激的长时程增强（LTP）也减少。M-1无效突变小鼠表现出正常或增强的记忆任务，涉及匹配到样本的问题，但他们严重受损的非匹配到样本的工作记忆以及巩固。我们的研究结果表明，M-1受体是专门参与记忆过程的皮层和海马体相互作用。
Blockade of cholinergic neurotransmission by muscarinic receptor antagonists produces profound deficits in attention and memory. However, the antagonists used in previous studies bind to more than one of the five muscarinic receptor subtypes. Here we examined memory in mice with a null mutation of the gene coding the M, receptor, the most densely distributed muscarinic receptor in the hippocampus and forebrain. In contrast with previous studies using nonselective pharmacological antagonists, the M-1 receptor deletion produced a selective phenotype that included both enhancements and deficits in memory. Long-term potentiation (LTP) in response to theta burst stimulation in the hippocampus was also reduced in mutant mice. M-1 null mutant mice showed normal or enhanced memory for tasks that involved matching-to-sample problems, but they were severely impaired in nonmatching-to-sample working memory as well as consolidation. Our results suggest that the M-1 receptor is specifically involved in memory processes for which the cortex and hippocampus interact.