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‘Dreamless’ mice in Japan help unravel the mystery of sleep

by Rowan Hooper

Special To The Japan Times

A dream can sometimes stay with us all day, perhaps even longer. Other times we wake up and don’t really remember much of what we’ve dreamed about. But what about other animals? Do they dream? It’s a question we’ll perhaps never be able to answer — but let’s give it a shot.

The logo for the International Institute for Integrative Sleep Medicine (IIIS) in Tsukuba, Ibaraki Prefecture, is a sleepy cartoon mouse curled up next to our planet. It is apt in two ways. First, while sleep is familiar to everyone in the world — and indeed to all animals — there is still a lot we don’t know about it. Second, the institute, based at the University of Tsukuba, aims to solve this mystery by using mice.

We spend approximately a third of our lives asleep, but exactly what sleep does for us is a mystery. Scientists assume there is something that builds up during our waking hours that makes us gradually more sleepy. If there is such a substance, however, we don’t know what it is.

When we want to investigate disease and general questions in biology, we tend to use animals as model systems. What often happens is that a scientist suspects a particular gene might be faulty and therefore be responsible for a disease, so mutates that gene in a mouse, fruit fly or worm, and then sees what happens.

However, Masashi Yanagisawa, director of the IIIS, takes a different approach.

Yanagisawa believes that starting with a particular gene in mind immediately biases the processes you are looking at. Instead, his team utilize what is called “forward screening.” In a gigantic research effort, they introduced random genetic mutations in more than 8,000 mice and then examined the animals for abnormal sleep patterns. To do this, they measured the brain waves of each sleeping mouse with electroencephalography (EEG).

Let’s just pause and think about this for a second. I know the scientists didn’t build a giant high-tech mouse dormitory with 8,000 tiny beds but, still, their achievement is remarkable. They have become extremely proficient at working with mice and fitting them with electrodes. Plus they have developed software that allows them to automatically screen the EEGs.

Yanagisawa’s team discovered two particularly interesting mutations. One made the mouse sleep for an extended period. The scientists called this mutation “sleepy.” Sleepiness was then traced to a gene called Sik3 that is active in neurons in the brain.

Another mutation gave mice a shortened and unstable sleep period. Sleep comes in cycles of rapid eye movement sleep and deeper, non-REM sleep where the eyes don’t roll around. Recent research has identified neural networks in different parts of the brain that switch us between wakefulness, REM sleep and non-REM sleep. However, the molecular mechanism regulating these switches was unknown. In particular, the REM part of the mouse’s sleep was disturbed. REM sleep is the part of the sleep cycle where most of the bizarre and vivid dreams occur. Mice without proper REM sleep were called “dreamless,” and have a mutation in the Nalcn gene. As a result, the massive screening process identified genes with roles in regulating the need for sleep and for maintaining periods of dream sleep. The work was published in the journal Nature.

While I can get my head around the idea of other mammals dreaming, it’s harder to imagine this in more “primitive” animals, but previous work has found similar mutations in genes related to Sik3 and Nalcn in fruit flies and nematode worms. The discovery that the genes have similar effects in animals as apparently different as invertebrates and mammals shows just how fundamental the process of sleep is.

“We hope that the discovery of these key genes is just the beginning of our long journey into the black box of sleep regulation,” Yanagisawa says. “It’s amazing that we know almost nothing about the simple question of what ‘sleepiness’ is physically in our brain. We will start from these genes and try to solve the great mystery.”

So to return to where we began: Do other animals dream? Naturally, we have no real idea and as far as worms and flies are concerned it’s impossible to say.

What about mice? I bet they do. Why not? They need to process and consolidate their memories, just like us, and they need to imagine the future. Perhaps they even have nightmares where they find themselves trapped in a room surrounded by hungry cats? Perhaps the mice in Yanagisawa’s lab in Tsukuba dream at night of a fabled land where everything is made of cheese?

When I asked Yanagisawa if he believed that mice dreamed, he was understandably reticent. “It’s difficult to answer since dreams are a fundamentally subjective phenomenon,” he says.

Rowan Hooper is the managing editor of New Scientist magazine. His new book — “Superhuman: People at the Extremes of Mental and Physical Ability” — will be published in May. Follow him on Twitter @rowhoop.