Scientists have known about the stage of sleep called rapid eye movement, or REM—which is associated with dreaming as well as improved learning and memory—since the 1950s. Many of its mechanisms remain mysterious, however. Now a study has identified two genes that play a key role in REM.
Mice that lack the genes Chrm1 and Chrm3 sleep fewer hours than typical mice and have almost undetectable REM levels, the researchers find. This is the first time scientists have homed in on genes essential for REM sleep, says Hiroki Ueda of Japan's RIKEN Center for Biosystems Dynamics Research, who conducted the study published in August in Cell Reports.
Ueda and his colleagues focused on the neural signaling chemical acetylcholine and its receptors in brain cells. Previous research had linked acetylcholine to REM sleep regulation, but Ueda's team wanted to find out which specific genes and receptors were involved. Using a variation of the gene-editing method CRISPR/Cas9, they produced seven mice lacking genes that encode different acetylcholine receptors. They measured REM and non-REM sleep in the genetically altered mice and in eight control mice, using electroencephalogram and electromyogram recordings.
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Mice without both the Chrm1 and Chrm3 genes slept less than the normal mice and got almost no REM sleep, the researchers found. Mice lacking only Chrm1 had shorter and more fragmented REM sleep; those without only Chrm3 had shorter non-REM sleep.
Yu Hayashi of the International Institute for Integrative Sleep Medicine at the University of Tsukuba, who was not involved in the study, says the results could mean that REM sleep is not necessary for survival; that the mutant mice somehow circumvent the need for it; or that the mice were engaging in REM sleep in deeper brain layers that the experiment did not detect. More research is needed to tease apart these possibilities.
Ueda says the findings could help illuminate sleep and mood disorders in people because REM sleep and its associated intense dreams are thought to affect depression and other illnesses.
