Do octopuses dream? Neural activity resembles human sleep stages

Benjamin Thompson

Welcome back to the Nature Podcast. This week, studying sleep in octopus brains...

Shamini Bundell

...and a hormone involved in weight loss. I'm Shamini Bundell...

Benjamin Thompson

...and I’m Benjamin Thompson.

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Benjamin Thompson

Sleep is an essential part of our lives. But it's not just the opposite of being awake. Sleep has different stages, when different parts of the brain are active. Generally speaking, last night, your sleep cycled between two phases: slow wave sleep, where the electrical waves in your brain synchronized in their frequency and things were pretty calm; and rapid eye movement or REM sleep when parts of the brain are incredibly active and the pattern of activity looks closer to when you're awake. It's during REM sleep that dreams can be a lot more vivid. It's not understood exactly what each of these phases are for. For example, slow wave sleep is thought to play a role in memory processing. But both phases must be important, because they're not just found in humans. In fact, studies have shown that two-stage sleep is found in a multitude of vertebrates: mammals, birds, reptiles, and so on, although there are differences between them. And recently, research has shown that this seems to be happening in some invertebrates as well. This week in Nature, a team have published some new work that delves deeper into one kind of invertebrate — the octopus — to learn more about what's going on in the sleep of these intelligent creatures. To find out more, I spoke with one of the authors of the paper Sam Reiter from the Okinawa Institute for Science and Technology in Japan. And he told me more about what is understood about invertebrate sleep.

Sam Reiter

Yeah, so previous work had showed that in invertebrates, it looks like there's not this sort of two stages of sleep rather than the brain of the Drosophila, for example, when it sleeps, really just kind of turns off. But some work a few years ago, suggested that in cephalopods, so this is octopus, cuttlefish and squid, there could be something like a more active stage of sleep. So cephalopods have their brains wired directly to their skin, to large sets of specialized skin cells that can expand and contract under neural control. So when you see the animal when they're awake, they're constantly changing their pattern for camouflage, and for social displays, and for hunting. What was reported was that while they're asleep, it looks like they are rapidly transitioning through these skin patterns, it doesn't look like the brain was turned off at all. And so this was very intriguing. And so this motivated us to delve deeper into what's going on. Is this really sleep? If it is, what's the meaning of these skin patterns? What's going on in the brain while the skin patterns are happening? These sort of questions.

Benjamin Thompson

And to get a sense of what was going on, then you were studying octopuses. Which ones in particular, were you looking at? What can you tell me about them?

Sam Reiter

So Okinawa has, I think, the greatest number of local octopus species on Earth, and we just happen to find this local species called Octopus laqueus first and brought them into the lab. And this species was a really fantastic choice for this question, because they're nocturnal, and they will sleep continuously during our day. So while we were at work, and it was really convenient to study their sleep.

Benjamin Thompson

And so it's known then that octopuses have these two sleep stages, what was not known about them what were you interested to find out?

Sam Reiter

Well, it hadn't been shown that active sleep met all the evolutionary conserved criteria for sleep. So there's three criteria that almost all animals that sleep show, and this state can be rapidly reversed, so this separates sleep from death. It comes with a heightened arousal threshold, so it's harder to wake this animal up from this state. And the third is that it's under homeostatic control. So if you prevent the animal from entering the state for some time, and then let them freely behave, they'll enter this state more often than they wouldn't before the deprivation. So we were able to show all three of these for the first time in octopus. So proving that this active state where the animal rapidly moves its eyes, rapidly transitions through skin patterns and does body twitches. This is actually sleep.

Benjamin Thompson

And that's the behavioural aspect of this work then, but you've also probed the brains of these animals to work out what's going on there. What did you find when you were reading the brain patterns of these octopuses that were asleep?

Sam Reiter

So in active sleep, the brain looks like it's awake, paradoxically. So the neural activity in certain brain regions during wake and active sleep match. In quiet sleep, the brain really kind of goes quiet, except for particular brain regions that have this 12 hertz short oscillatory bursts that resembles what we see in vertebrate slow wave sleep. And these are features linked with learning and memory in vertebrates. And intriguingly, they're only found in octopus in regions that we know have been linked to learning and memory. So we don't know quite what the significance of this is. But it's an intriguing finding, I think.

Benjamin Thompson

So it seems like you've shown that these octopuses have these two sleep stages, active sleep and quiet sleep. And during the active sleep, their brains are acting like they're awake. And you're seeing some of this play out on the skins of the animals, right, with a pattern changes, as you mentioned earlier on, what did this tell you?

Sam Reiter

So the active sleep skin patterns, we could record these, and we can also record the patterns when the animal's awake. And we find that these patterns matched almost exactly. So it seems that the octopus when it's asleep, is reactivating, its waking skin patterns. This is accompanied by wake-like neural activity. So the significance of this is unclear, we had a number of different hypotheses. So I guess from maybe the least to the most interesting. One is that it could be just all the individual cells in his body are doing different sort of offline practice to maintain the neural connections, just a housekeeping sort of function. Little more interesting of an idea would be that this is an offline practice of the functions of the skin patterning system. So in vertebrates, when you learn some motor skill, your brain is reactivating those motor circuits offline to help you better learn the skill. Or it could be that this is something like the reactivation of the waking experience in the octopus for something like memory consolidation, or even something like dream. So I think this is the full gamut of what's possible here. And I think future work, hopefully, we'll narrow it down.

Benjamin Thompson

And what do you think octopuses might be dreaming about? If that's what it is.

Sam Reiter

Well, you know, we can see the patterns that they do when they're awake. And we can associate those with certain situations. So there's definitely a pattern that they do when it seems like they're happy when they get some food. Those patterns show up when they're sleeping. So it's tempting to say this is the contents of the sleep, but it could be something else. But the fact that we can map these sleeping patterns onto waking patterns means that the octopus gives us really a unique window into the contents of the offline brain. It's a unique access that would be difficult to come by, by studying other animals. So it might be that that octopus will help us understand what's going on, and this enigmatic area of sleep research.

Benjamin Thompson

And more broadly, you've looked at this in a group of animals that diverged from vertebrates, hundreds of millions of years ago. They are a vastly alien species compared to you, or I, for example. And yet, it seems like there are some parallels that you could draw between the two, right? Like humans have the REM sleep and the slow wave sleep, and octopuses have the active sleep or there's a lot going on in the brain and the quiet sleep where things a bit more placid. Is it possible to draw a parallel between the two do you think?

Sam Reiter

So the range of similarities that we observe, I think, suggests that this is an example of convergent evolution. Where, as you say, our common ancestor lived 550 million years ago, and almost certainly didn't do this. So this is two paths that evolution has taken and has emerged at sort of a common form of sleep. So this, to me suggests that whatever sleep and these two stages of sleep is for, it's something quite fundamental that evolution would hit upon it twice independently. And it could mean that these two stages of sleep and large brains and complex behavior, which has only evolved twice in the vertebrates, and in the cephalopods, maybe these things aren't go hand-in-hand. But you know, future work is needed to determine this.

Benjamin Thompson

And in terms of your work with the octopuses, then where does it go next?

Sam Reiter

I think the interesting directions are how mechanistically do these two stages of sleep, alternate and be generated? And how does this map onto what we know mechanistically about the mammalian two stage sleep, for example. And then I think, maybe even more interesting is can we do the sort of functional tests that have been done in mammals to try to establish what these two stages of sleep are for, what benefit they give the animal. If these tests also show some sort of parallel answer, then it really points us towards a kind of an explanation for this in terms of convergent evolution of common function.

Benjamin Thompson

I mean, what does it make you think about the universality of sleep because there's so much we don't know about it as a process?

Sam Reiter

I think sleep is quite universal. It seems like every animal from jellyfish to hydra to humans sleeps. Two stages of sleep it was thought to be a human and then a vertebrate specific phenomenon. But now there's this work in cephalopods. There's some suggestive work in spiders. It could be the two stages of sleep is also quite broad. Again, it cries out for some explanation for why.

Benjamin Thompson

Sam Reiter there. To read his paper head over to the show notes for a link. We've also got a video about the work on our YouTube channel. So if you want to see the patterns flashing across a sleeping octopus's skin, look out for a link in the show notes once again,

Shamini Bundell

Coming up a hormone that could help make diets more effective. Right now though, it's the Research Highlights with Dan Fox.

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Dan Fox

Last year's massive eruption of an underwater volcano in Tonga produced the most extreme lightning ever recorded. The volcano Hunga Tonga–Hunga Ha‘apai set or tied many records when it erupted in January 2022. Its ash plume soared 58 kilometers into the air, and it created the most powerful atmospheric waves of modern times. Now, researchers have combined data from weather satellites and ground-based radio antennas used to detect lightning to peer into the ash cloud and study the powerful thunderstorms that were triggered by the eruption. They found that at the peak, the storm has generated a record 2,615 lightning flashes every minute. Lightning also formed in huge concentric rings up to 280 kilometers across, which expanded and contracted as turbulence rippled through the atmosphere. Read that research in full over in Geophysical Research Letters.

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Dan Fox

A new nylon-based fabric can be fashioned into a garment that keeps the wearer either warm or cool at the flick of a switch. The material is made a thin layers of nylon, gold, and an electrically conducting polymer. To make the material flexible, the author's used principles from the Japanese paper art kirigami, which entails cutting a 2D surface and then folding it into 3D patterns. The polymer can either emit heat or provide insulation depending on the voltage applied to it. Tests showed that a person wearing a patch made of the material would feel the same skin temperature at ambient temperatures from 22 degrees Celsius down to 17.1 degrees. Something that would take a lot of energy to achieve a conventional electric heater for example. The authors say that materials such as theirs could help to limit the occurrence of medical events such as stroke that are linked to changes in body temperature. You can find that paper in PNAS Nexus.

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Shamini Bundell

Next up on the show, you may well be familiar with dieting. In its simplest form, it refers to calorie restriction in order to lose weight. But you may also be familiar with the fact that weight loss can be quick at first, but then can slow down and weight can even creep back on even when calories remain reduced. The problem is that metabolism isn't a constant and the body adapts. When food becomes scarcer, the body aims to start using energy more efficiently in response. For example, some adipose tissues, fats, can reduce their output of heat, conserving precious energy stores. However, the exact mechanisms underpinning this effect, especially in humans, are unclear. Now though, in Nature, there's a new study describing how researchers have found that a hormone known as GDF15, may be able to prevent this adaptation and allow continued weight loss. Reporter Nick Petrić Howe how called up Greg Steinberg, one of the study's authors, and started by asking him what the motivation was for this study.

Greg Steinberg

We started from the observation people can lose weight quite easily, initially, but over time, that ability to lose weight plateaus, and then most people regain the weight within a year, right. Dieting and exercise we know works. But for most people, it's not maintained. And it's not because people are weak-willed and don't know what they're doing. They have the best intentions, but their metabolism slows down and is working against them. And so this was the motivation for this.

Nick Petrić Howe

And so you were looking at this plateauing then, and you look to something called a GDF15 How did you get to GDF15? And what is it?

Greg Steinberg

Well, many years ago, we pulled GDP15 out a screen where we were looking for how metformin, the leading type 2 diabetes medication might be signaling to the rest of the body. And we discovered that GDF15 was being secreted from the liver, and then talking to the brain to tell the brain to reduce feeding. Subsequently, after we did those studies, very shortly after that, we found out that many companies were working on GDF15 as an anti-obesity agent. And this is really how we got into studying this, whether there might be other beneficial effects of GDF15, beyond appetite control.

Nick Petrić Howe

Okay, so at the start, it was just seen as maybe an appetite suppressive, it would stop people, or mice, I guess in these cases, eating.

Greg Steinberg

That's exactly right. And, you know, people have done studies in mice, non-human primates and even clinical studies with GDF15 showing that it can suppress food intake.

Nick Petrić Howe

And so to further look into what GDF15 can do, what did you do in this study?

Greg Steinberg

So what we did is we repeated a study that was done four years ago, started injecting mice with the same doses of GDF15, but had a calorically matched group of animals. And we did this initial experiment at a temperature range called thermal neutrality, which is a range of temperature that slows down the metabolism of the mouse, similar to humans. And what we found is that when we did that, you know, we replicated the previous finding exactly. The first 14 days of treatment, the calorically-restricted mice, and the mice injected GDF15 lost the exact same amount of weight, which was exactly what the previous studies had published on showing that GDF15 was only regulating appetite. But what we found was after 14 days, the calorically-restricted mice plateaued, they continue to eat a small amount of food like 10 or 13%, less food, but their bodyweights plateaued. They no longer lost any more bodyweight, while as the GDF15 mice continued to lose bodyweight, suggesting that there was another mechanism besides food intake.

Nick Petrić Howe

So what role then was GDF15 playing to sort of prolong this weight loss?

Greg Steinberg

That was the exciting bit that we then pursued and found that, in fact, what was happening is when we were delivering GDF15 to mice, that their metabolism wasn't slowing down to the same extent is the calorically-restricted mice.

Nick Petrić Howe

And you did a whole host of studies to find the mechanism for how GDF15 was preventing this slowdown in metabolism normally associated with calorie restriction. And your initial focus, as I understand it was on adipose tissues, on fat.

Greg Steinberg

We really expected this to be the mechanism. But we could see no signs that GDF15 was stimulating energy expenditure in adipose tissue, which then led us to investigate the muscle. And with that, we found that theGDF15 was in fact stimulating energy burning within the muscle. And it was doing so by making the amount of calcium cycling in the muscle be enhanced. So it was reducing the efficiency in which the muscle sequesters calcium when it contracts.

Nick Petrić Howe

And this in effect made the metabolism higher, I guess, to put it crudely.

Greg Steinberg

Yeah, that's exactly right. And you know, there have been studies published in humans remarkably, where, when people undergo weight loss therapy, or dieting, and they go on an exercise bike, and exercise at a set workload, their muscles actually become more efficient after the weight loss. And we think this is all to do with the improved calcium cycling, the efficiency of the calcium cycling. So when you move, you're burning less calories, because the system has become more efficient in sequestering that calcium with muscle contractions.

Nick Petrić Howe

And speaking of humans, do you think there is an opportunity here to use this GDF15 to help people who struggle with weight loss?

Greg Steinberg

Our studies really suggest that the biggest effect with GDF15 is actually going to be in the context of which dieting is also being used. GDF15 on its own isn't enough to increase energy expenditure above baseline levels. But what it will do is it will prevent the slowdown in metabolism that occurs with dieting or caloric restriction. And this is quite important in the context of we now have a series of drugs that suppress feeding and these drugs have been very successful that are causing weight loss. So in the context of using GDF15, it may be more effective when used with either a dieting regime, or with a caloric- suppressing agent because it will keep that energy burning high.

Shamini Bundell

That was Greg Steinberg from McMaster University in Canada. To find out more about this study, check out the show notes for some links.

Benjamin Thompson

Finally on the show, it's time for the Briefing Chat, where we discuss a couple of stories that have been highlighted in the Nature Briefing. And Shamini why don't you go first, this week. And it's a story that, well, you know quite a lot about.

Shamini Bundell

It is, I'm cheating again, it's another story that I'm going to tell you about, because I have made a video about it. It's out on our YouTube channel right now. But it is very cool story. And it is a paper that was out last week in Nature Communications Engineering, actually out on International Women in Engineering Day. And it is all about what I like to call a little robotic raspberry.

Benjamin Thompson

A robotic raspberry. Okay, well listen, you've got to unpick this a little bit, Shamini, tell me about the robotic raspberry.

Shamini Bundell

So it looks like a little fake raspberry. It's very cute. It's slightly red. And it's got like a bumpy outer surface. And this is what this paper is about the development of, they call it a physical twin. And the idea is basically this story is all about trying to create and develop and train fruit-picking machines. So in this case, a raspberry-picking robot. How do you train a robot to be good at picking raspberries? And apparently, that's not that easy.

Benjamin Thompson

Yeah, because raspberries are quite squishy fruit.

Shamini Bundell

They are.

Benjamin Thompson

If you get a robot to go up there and just kind of take its pincers, and squeeze, you're going to have a raspberry smoothie rather than a picked raspberry.

Shamini Bundell

There's quite a lot of squishiness involved, yes, in raspberry picking. And you know, there's loads of sort of fruits and vegetables and crops that are all harvested by machine or at least like a lot of the food we consume comes from this sort of machine harvesting. But yeah, certain soft fruits, it's a bit trickier, raspberries being one of those. And the way to develop machines that are better at picking raspberries is you have to train them up and test them and and get them better at it. And that involves going into a raspberry field in raspberry season, and testing out your robot.

Benjamin Thompson

Right.

Shamini Bundell

But transporting your robot out into the field having this limited amount of time. That's a bit tricky. So what these researchers have done is they've said, well, what if we could just train and, sort of, work on our robot in the lab before having to go and actually test it in the field? And let's just set up in the lab, a fake raspberry bush that we can work with.

Benjamin Thompson

Obviously, of course, right? Why wouldn't you? And so the fake robotic raspberry then is helping the robot learn how to not squeeze too hard. Is that right?

Shamini Bundell

Yeah. So it's not, you know, just to sort of solid, raspberry shape. It does what a raspberry does you know, when you pluck it from the stem, and the soft fruity bit is round the outside and there's a sort of bit of the stem that goes down into the middle and the stalk sort of bends slightly, and then you kind of pull and then you get the raspberry in your hand. I don't know if you picture any raspberries in your time?

Benjamin Thompson

I can't say I have, but you're describing a beautifully. But okay, all right. So there's a trick to that is what you're saying.

Shamini Bundell

There is a trick to it. And the key thing was what they did was they got humans to pick the fake raspberry off its little plastic stem. And this robotic raspberry has a sensor in it. So it can detect pressure and sense the pressure. And then what they did was they said, Okay, well, let's look at exactly what humans and expert raspberry pickers are doing when they pick a raspberry. And it turns out that what they're doing is putting that pressure on, pulling and then as soon as it kind of comes off, lightening up the grip so that that raspberry doesn't get crushed. And once they have the readings from the raspberry picking experts, they can then feed that back into what the robot is doing and give it that feedback and say, 'oh, you're going a bit hard there, or a bit gentle there.' And actually, again, use this pressure sensor to tell the robot how it's doing. And thus sort of improve it over time.

Benjamin Thompson

Right and so the robot I guess then practices on the fake sensor-laden raspberry then. And then it's brought out into the field and actually had a go on the real thing.

Shamini Bundell

Yeah, so they had some lovely footage of them actually testing with this robot, sort of trundling down the rows between all the raspberry plants growing and having a go at plucking the raspberries off the stem, which from the video, it seems to have done pretty well. They said that they were pleasantly surprised by how well it did just given that that was the first time actually that it was meeting real raspberries.

Benjamin Thompson

And where to next then? I mean, is this robot ready for primetime?

Shamini Bundell

I don't think this robot is at the stage of mass production and commercialization yet, I think that's the sort of idea of a lot of the research to be able to sort of mechanize these processes. This has various benefits, including preventing food waste that can occur when there are labor shortages. But in order for these particular machines to be ready for that there's more angles that this group haven't looked into. So for example, robot vision, so how these machines actually spot a raspberry you know, how does that find it to to grasp it? And kind of detect the ripeness maybe from the color, things like that. But you know, this work kind of wasn't really in a way about the raspberry-picking robot. It was about making this fake raspberry, this physical twin as they call it, so that they or other teams can do all this work in the lab, work on these robots and get them to a much more advanced state before going out into the field and plucking fruit.

Benjamin Thompson

Well, a fascinating piece of research, no doubt and listeners head over to the show notes where you can find a link to watch a video all about the fake fruit, the robot raspberry and the picking robot as well. Well, listen let's move on in today's Briefing Chat and I've got a story that I read about in Nature. And I'll start with a question and that is 'What does a bad house party and the exoplanet TRAPPIST-1 c have in common?'

Shamini Bundell

This is not a serious question? This is gonna be some kind of terrible pun.

Benjamin Thompson

Well, I mean, however, did you guess? The answer is neither of them have much of an atmosphere. And bringing it back to seriousness of course this is some research that was published in Nature and it's about a team who have used the James Webb Space Telescope, the JWST to have a look at this exoplanet. As I say the results reveal there's really not much of an atmosphere there if there is one at all.

Shamini Bundell

Okay, so TRAPPIST-1 c, the TRAPPIST system that sounds familiar to me. Can you just give me a bit of background on where and what this exoplanet is? And why were researchers interested in looking for an atmosphere there in the first place?

Benjamin Thompson

Well, that's a great question. The TRAPPIST-1 system then is kind of the poster system for kind of studying exoplanets, right. And so it's some 40 light years away, and it has seven of these planets orbiting the star, right. And these have rocky surfaces, roughly the same size as Earth. And so researchers have been looking at this system to see how planets form and evolve and and maybe how they become habitable. But of course, you know a part of that is looking to see if they've got a thick atmosphere. And a few months ago, researchers saw that the closest planet to this star which is TRAPPIST-1 b okay, they've had a look at that, and there is no substantial atmosphere there, right. And JSWT lets researchers look for atmospheres in greater detail than other observatories like Hubble, okay. And I think the problem with the 1 b is that the star that it orbits around, it's a cool star, and it blasts out loads of ultraviolet radiation. And this just batters the closest planet and stripped away the atmosphere. So researchers went to the next closest, which is 1 c to see if, you know, maybe it was far enough away to kind of get away with it, to have some sort of atmosphere. But it seems like that's not the case.

Shamini Bundell

And how do they actually know that there's no atmosphere there now?

Benjamin Thompson

Well, by having a good look at this exoplanet then, this TRAPPIST-1 c, they were able to calculate the surface temperature of this planet. And for the side that faces the sun, it showed that the surface temperature was about 107 degrees Celsius, and I find it incredible, they could figure that out from so far away. But this makes it too hot to maintain a thick carbon dioxide rich atmosphere. And the reason this is interesting is because a lot of researchers thought this exoplanet 1 c might be like Venus, okay, because it's about the same sort of size, it receives about the same amount of solar radiation. But whereas Venus has this very thick carbon dioxide atmosphere, that is not the case for the exoplane. And they went on this more modeling as well. And their results suggest that this exoplanet then only had a low amount of water when it was formed, okay, so I think less than ten Earth oceans' worth of water. And so combining this with the lack of the CO2 atmosphere suggest that TRAPPIST-1 c never had many ingredients for habitability.

Shamini Bundell

No aliens, no future human space colony on TRAPPIST-1 c.

Benjamin Thompson

Well, I mean, we don't know, for example, that there's no atmosphere at all, there could be a thin atmosphere, but not the kind of thick one that was being posited. But what gets interesting then is the researchers in the article so that it might make a difference to the amount of planets which are actually habitable because planets of this type are quite common around many stars. But showing that, you know, in this case, there's no atmosphere could reduce the number of you know, the probability of finding a habitable exoplanet somewhere else. But it's not necessarily the end of the story. Because as I say, TRAPPIST-1 system has seven planets. We've looked at B and C...

Shamini Bundell

Oh, D, E, F, oh, there's a whole load left to go then.

Benjamin Thompson

Yep.

Shamini Bundell

Okay. Is that the next stop for the JWST's gaze?

Benjamin Thompson

Well, definitely researchers are keen to have a look. And a paper it was posted to arXiv a little while ago, so it's not a peer-reviewed paper, doing a bit of maths and saying that maybe the fourth and fifth furthest planets in the TRAPPIST-1 system, so that's e and f for those of you at home keeping score, could still have thick atmospheres because they sit far enough away to avoid you know, having it blasted away like b and c. So there's so much we don't know about how you know exoplanets form and how their atmospheres form. But it seems like TRAPPIST-1 is helping researchers out.

Shamini Bundell

Well, we love a space story. Thank you for that, Ben. And listeners, if you wanna find links to these two stories we've been talking about. We'll stick those in the show notes, as well as a sign-up link for the Nature Briefing, which is an email newsletter with lots of exciting stories like these.

Benjamin Thompson

And that is it for this week's show. But of course, just time to say you can reach out to us on Twitter, we're @naturepodcast, or send an email to podcast@nature.com. I'm Benjamin Thompson.

Shamini Bundell

And I'm Shamini Bundell, thanks for listening.