Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep
Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep
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DOI：
10.1016/j.celrep.2018.07.082
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发表时间：
2018-08-28
期刊：
影响因子：
8.8
通讯作者：
Ueda, Hiroki R.
中科院分区：
文献类型：
--
作者：
Niwa, Yasutaka;Kanda, Genki N.;Ueda, Hiroki R.
睡眠调节涉及分布在大脑区域的特殊神经元之间相互依赖的信号。虽然乙酰胆碱促进觉醒和快速眼动（REM）睡眠，但由于神经回路和分子的冗余，尚不清楚胆碱能通路是否对快速眼动睡眠至关重要（即绝对必要）。首先，我们证明TrkA+胆碱能神经元的突触抑制导致严重的短睡眠表型，睡眠减少主要归因于黑暗期睡眠时间的缩短。随后通过三靶CRISPR方法全面敲除乙酰胆碱受体基因，发现敲除两种gq型乙酰胆碱受体Chrm1和Chrm3时出现了类似的短睡眠表型。引人注目的是，Chrm1和Chrm3双敲除会长期减少REM睡眠，几乎无法检测到。这些结果表明，毒蕈碱类乙酰胆碱受体Chrm1和Chrm3对快速眼动睡眠至关重要。
Sleep regulation involves interdependent signaling among specialized neurons in distributed brain regions. Although acetylcholine promotes wakefulness and rapid eye movement (REM) sleep, it is unclear whether the cholinergic pathway is essential (i.e., absolutely required) for REM sleep because of redundancy from neural circuits to molecules. First, we demonstrate that synaptic inhibition of TrkA+ cholinergic neurons causes a severe short-sleep phenotype and that sleep reduction is mostly attributable to a shortened sleep duration in the dark phase. Subsequent comprehensive knockout of acetylcholine receptor genes by the triple-target CRISPR method reveals that a similar short-sleep phenotype appears in the knockout of two Gq-type acetylcholine receptors Chrm1 and Chrm3. Strikingly, Chrm1 and Chrm3 double knockout chronically diminishes REM sleep to an almost undetectable level. These results suggest that muscarinic acetylcholine receptors, Chrm1 and Chrm3, are essential for REM sleep.