RRC ID 54168
Author Niwa Y, Kanda GN, Yamada RG, Shi S, Sunagawa GA, Ukai-Tadenuma M, Fujishima H, Matsumoto N, Masumoto KH, Nagano M, Kasukawa T, Galloway J, Perrin D, Shigeyoshi Y, Ukai H, Kiyonari H, Sumiyama K, Ueda HR.
Title Muscarinic Acetylcholine Receptors Chrm1 and Chrm3 Are Essential for REM Sleep.
Journal Cell Rep
Abstract 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.
Volume 24(9)
Pages 2231-2247.e7
Published 2018-8-28
DOI 10.1016/j.celrep.2018.07.082
PII S2211-1247(18)31200-2
PMID 30157420
MeSH Acetylcholine / metabolism* Animals HEK293 Cells Humans Male Mice Mice, Inbred BALB C Mice, Inbred C57BL Mice, Knockout Receptor, Muscarinic M1 / metabolism* Receptor, Muscarinic M3 / metabolism* Sleep, REM / genetics*
IF 8.109
Times Cited 12
Mice RBRC02958