How to Sleep: Ability to Dream May Be in the Genes

In recent decades our understanding of sleep has significantly improved, however, there is still much that remains a mystery.

We know that in mammals and birds, it is split up into two alternating modes: REM (Rapid Eye Movement) and non-REM sleep. Scientists think that the REM stage—during which the brain is as active as it is during wakefulness—plays an important role in maintaining brain function and physical wellbeing. It is also the period when most dreams occur—in humans at least.

So far, the biological underpinnings of REM have remained poorly understood, but now, a study published in the journal Cell Reports has demonstrated how a key pair of genes regulate the amount of REM and non-REM sleep that an animal experiences.

A team led by Hiroki Ueda at the RIKEN Center for Biosystems Dynamics Research in Japan found that mice which had been genetically engineered to lack two specific genes largely did not experience REM sleep.

"Sound sleep is essential to the quality of human life, while some impairment in sleep may lead to various untoward consequences," Ueda told Newsweek. "However, its molecular machinery largely remains to be revealed hindering the development of treatments for sleep-related diseases," he said. "We tried to identify genes specifically working in the brain regions involved in sleep."

Previous research has shown that a neurotransmitter—the body's chemical messengers which transmit signals through the brain and nervous system—known as acetylcholine and its receptors are important for the regulation of REM sleep.

Large quantities of acetylcholine are released in certain regions of the mammalian brain both during REM sleep and wakefulness. But scientists have been unable to identify which receptors—proteins which neurotransmitters can bind to, enabling communication between cells—are directly involved in regulating REM sleep.

In their research, the scientists knocked out several different genes in the mice which are responsible for the development of various acetylcholine receptors, one-by-one. They found that the loss of two receptors—known as Chrm1 and Chrm3—which are common in certain brain regions, had a significant impact on sleep in the mice.

When Chrm1 was knocked out, the amount of REM sleep in the mice was reduced and fragmented. On the other hand, when Chrm3 was knocked out, the length of non-REM sleep was reduced. When the genes responsible for both receptors were knocked out simultaneously, the mice experienced almost no REM sleep at all.

Mice and humans share the genes that are responsible for the Chrm1 and Chrm3 receptors. So in a hypothetical situation, individuals genetically engineered to lack them would likely not experience REM sleep either and would probably also not be capable of dreaming normally.

"This would be an interesting question to be investigated in future studies," Ueda said. "If pharmaceutical companies develop a specific inhibitor to these receptors, Chrm1 and Chrm3, I am quite sure that human will also demonstrate a similar REM-less phenotype."

"Regarding the genetic study, it is virtually impossible to conduct genetics with humans as we did with mice, and only human subjects can be interrogated for dreams," he added. "This is why it is very difficult to investigate the molecular mechanisms behind dreams."

Interestingly, the mice who didn't go through REM sleep survived nonetheless. This surprising finding could enable researchers to understand more about what role the sleep phase plays in biological functions, such as learning and memory.

"The apparent soundness, at least superficially, of the double-knockout mice is surprising even to us," Ueda said. "However, please keep it in mind that the mutant mice survived in laboratory conditions with sufficient food and without any enemies."

"In a wild environment, these genes would be important for survival," he said. "This unexpected viability despite the almost completely abolished REM sleep, in future work, will allow us to rigorously verify whether REM sleep plays crucial roles in the life-support functions of organisms."

The discovery that Chrm1 and Chrm3 play a key role in REM provides important insights into this mysterious sleep phase and could have important implications, according to the researchers.

"REM sleep is closely correlated with psychiatric disorders including PTSD (post-traumatic stress disorder), which is accompanied by bad dreams," Ueda said. "The identification of components indispensable for REM sleep such as Chrm1 and Chrm3 reported in this project, may help, for example, to refine antidepressants for treating the bad dreams of PTSD patients."