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Genetic snooze button shows that broken sleep impairs memories

Not Exactly Rocket Science
By Ed Yong
Jul 26, 2011 12:00 AMNov 20, 2019 3:42 AM


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Many mental disorders can disrupt the sweet embrace of a long, continuous sleep, including alcoholism, depression, Alzheimer’s and parenthood. And that’s bad news. We know that a good night’s sleep helps to solidify our memories of the previous day’s experiences. And according to a new study, we need a certain amount of continuous sleep for those benefits to kick in. From an evolutionary point of view, it seems strange that we sleep for hours on end. Rather than leaving ourselves unresponsive and vulnerable for large chunks of time, why not simply sleep over several shorter fragments? This is not an easy question to answer. Until recently, it has been all but impossible to break up the continuity of sleep without also affecting its quality, or stressing out the animals in question. But Luis de Lecea from Stanford University has found a way. He has engineered mice with in-built silent alarm clocks. These animals can be woken up at will with a pulse of light delivered directly to their brains. De Lecea focused on a group of neurons that exude a hormone called hypocretin (Hcrt), which helps to rouse a sleeping animal. In 2007, he loaded the Hcrt neurons of mice with a light-sensitive protein called Chr2. De Lecea used an optic fibre to shine blue light onto Chr2, causing the Hcrt neurons to fire, and the sleeping mice to wake up. This is just one of the many applications for optogenetics, the exciting new field where scientists can control the behaviour of animals and cells using bursts of light. Asya Rolls, who is part of de Lecea’s team, used this technique to gently wake her mice once a minute, without actually disrupting the overall quality of their sleep. The rodents’ brain waves revealed that they did indeed start to wake up, before falling asleep again in less than two seconds – a so-called “microarousal”. Their sleep became fragmented, but they slept for the same amount as their undisturbed peers. Their brainwaves showed that they were sleeping just as deeply, and they spent the same amount of time in the two major phases of sleep – REM and non-REM. The levels of stress hormones in their blood didn’t go up, and they showed no signs of stress or groggy behaviour when they finally woke up. Rolls had essentially invented the world’s least annoying snooze button. For all intents and purposes, the mice had had a good night’s sleep, albeit one that was broken up into several small chunks. But that made a lot of difference. Before the mice had their naps, Rolls placed them in an arena with two similar objects, which they explored equally. Half an hour later, they were sent to sleep and half of them were briefly woken up with blue light every minute. After four hours of this, they were placed back into the arena, where they saw one of the two objects from before, along with a completely new one. Mice are drawn to new things and the undisturbed individuals spent around 70% of their time looking at the new object. But those whose sleep had been broken up spent just as much time with each object; they didn’t remember which one they had seen before. However, if Rolls woke the mice up every two minutes, they had no problems remembering which of the two objects was familiar. This suggests that mice need to sleep for between one and two minutes straight, if they are to consolidate newly formed memories. It’s hard to say what the equivalent amount of time is for humans. Mice tend to have short sleep cycles of around 9 minutes, while the equivalent for a human is 90 minutes. De Lecea says, “I prefer not to speculate about the minimal sleep unit in humans, but patients with sleep apnea with severe sleep fragmentation (more than 30 waking moments per hour) tend to have memory deficits.” This link between sleep and memory is now becoming very clear. Sleep allows us to prune away any new connections between our brain cells, leaving behind the most useful ones. It also gives us time to replay the events of the day before, fitting new information in among the old, and solidifying our latest experiences into long-term memories. By briefly disturbing her mice, Rolls thinks that she interfered with these replays, preventing the animals’ brains from consolidating what they learned. Slowly, science is waking up to the purpose of sleep, and new genetic techniques are speeding up the pace of such discoveries. Just a month ago, I wrote about the work of Jeffrey Donlea, who has genetically engineered flies that he can send to sleep by raising the temperature. He found that the insects developed stronger memories after they’d had a nap. Meanwhile, a Japanese team have developed mice that they can similarly send to sleep on demand, by using bursts of light to switch off their hypocretin neurons. And Rolls has just showed how important it is to get unbroken bouts of sleep, regardless of the total amount. Reference: Rolls, Colas, Adamantidis, Carter, Lanre-Amos, Heller & de Lecea. 2011. Optogenetic disruption of sleep continuity impairs memory consolidation. PNAS http://dx.doi.org/10.1073/pnas.1015633108More on optogenetics:

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