How an increased heart rate could induce anxiety in mice

Host: Shamini Bundell

Welcome back to the Nature Podcast. This week, why increasing a mouse's heart rate can make it feel anxious.

Host: Nick Petrić Howe

And how the DART mission managed to move an asteroid. I'm Nick Petrić Howe.

Host: Shamini Bundell

And I'm Shamini Bundell.

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Host: Shamini Bundell

First up on the show this week, we know that emotions can induce changes in the body, but new research is showing how changes in the body might be inducing emotions. Benjamin Thompson is here with the story.

Reporter: Benjamin Thompson

Have you ever got so anxious that you felt your heart start to race? It's something that many of us have experienced, and it can be frightening. The effect that emotional states like anxiety have on organs like the heart, and the ways they do it are well explored. But what about the other way round? It's a question that physiologists, philosophers, and psychologists have puzzled over for a very long time, as Karl Deisseroth from Stanford University in the US explains.

Interviewee: Karl Deisseroth

I think it was articulated very well by William James in 1884, he wrote a famous essay called What is an emotion?. You could put his question very succinctly as maybe we feel sorry because we cry, maybe we're afraid because we tremble, so do we feel anxious because the heart is beating more quickly and more powerfully? This was a very intriguing concept, but very hard to test directly.

Reporter: Benjamin Thompson

One of the reasons it's been hard to test directly whether heart rate can induce emotions like anxiety, is due to the fact that many of the methods to modulate our heart’s beats-per-minute, can be nonspecific, and affect other parts of the body, making it difficult to pinpoint if heart rate itself is playing a direct role on emotional state. But this week, Karl and his colleagues have shown a way to do just that in mice, and shown that physiological states in the body can affect emotional states in the brain. Central to their finding is a technique that Karl pioneered in the mid-2000s, called optogenetics, in which the activity of cells can be controlled by light sensitive proteins. In this case, the team made an optical pacemaker. This worked by using light to stimulate mouse heart-cells that had been engineered to react to red light. This activation could happen from outside the body, so no surgery or other invasive technique was required.

Interviewee: Karl Deisseroth

So now we can outfit mice with a little vest with a light source, and we can pace their heart precisely. Primary direct control on the heart contraction, and we were able to ask the question – does this affect the emotional state? And it turned out, it did, but with a twist.

Reporter: Benjamin Thompson

In one set of experiments, the team briefly increased the heart-rate of mice by about a third, from a mouse's baseline of 660 beats per minute, up to 900 beats per minute, and cycle this change every couple of seconds. But this increase on its own didn't produce any anxiety related behavior.

Interviewee: Karl Deisseroth

If the animals were in a non-threatening environment, there was no effect of pacing the heart at higher rates. But if the animal was in a anxiety-provoking environment, then pacing the heart substantially increased the anxiety-related behaviors of the animal.

Reporter: Benjamin Thompson

These anxiety-provoking environments included tests in spaces with exposed sections and areas where the mice could hide.

Interviewee: Karl Deisseroth

And just by the intervention of pacing the heart at a higher rate, it made the animals withdraw from the exposed environment, far more than they would have otherwise and effectively hide in a perceived safer environment. So, the animal's behavior reports to us on its inner state.

Reporter: Benjamin Thompson

And what's more, Karl says that this switch in behavior happened immediately in mice when their heart rates were increased. To get an idea of what might be underlying this shift in behavior, they looked in the mouse's brains to see what areas were being activated.

Interviewee: Karl Deisseroth

And we found big changes in a couple regions, one was the insular cortex or the insula. This was previously known anatomically to be connected to receiving some of this feedback of information from the body. So of course, the brain keeps track of a number of things in the body, how full the stomach is, things like that, and so there's a lot of information that comes back from the body to the brain, and a lot of this was known anatomically to go through the insula.

Reporter: Benjamin Thompson

Inhibiting activity of this area reduced the effects of increased heart rate on anxiety-like behavior in the mice. Taken together, the results suggest that, in certain situations, heart rate can affect anxiety, in mice at least, and that the insular cortex is an important mediator to this happening. Anna Beyeler from the French National Institute of Health and Medical Research works on the neural circuits of behavior and has written a News and Views article about the research. She thinks that these findings provide insights into how emotions work, but there are more questions to be answered. Interviewee: Anna Beyeler

It's a demonstration that just changing one parameter — the heart rate — can induce anxiety, so this is quite important. And then I think it's super interesting that they identify the posterior insula as a key relay for that behavior. At least to me what the most interesting next question would be is the timing of this interaction from the heart to the brain and then to emotion. Here the increase heart rate is 36% above normal frequency, so they have shown that it impacts straightaway, so if we do only a 10% increase, but constantly, how does that impact behavior?

Reporter: Benjamin Thompson

Anna is also intrigued about the role development plays. Would chronic heart rate increase early in a mouse's life affect its anxiety-related behaviors later on, for example? For Karl too, there are lots of things left to understand about the specifics of the mechanism, and whether other large organs like the gut or the skin can elicit emotional states in the brain. There's also the big question of whether what they found is relevant to humans. But he thinks it could ultimately help in the development of new treatments.

Interviewee: Karl Deisseroth

The confidence of standing on this firm causal foundation could help us refine both behavioral therapies and medication induced therapies, because now you can envision targets that are peripheral, that are in the body as strategies for modulating brain states. Of course, this is a very early days, and I couldn't be certain that such an effect would be clinically useful, but in terms of opening our eyes to a new way of looking at things, this sort of discovery is, I think, illuminating.

Reporter: Benjamin Thompson

For decades, researchers have debated whether states in the body can induce emotions, but for Karl, this work demonstrates that there does appear to be a link, and for him, it means that when it comes to emotions, researchers need to consider the body as a whole.

Interviewee: Karl Deisseroth

I think a lot of people have thought hard about this over the many years since William James, and nobody denies that the brain affects the body, nobody denies that the body affects the brain, but the outcome of an experiment like this was very much unclear. Would purely pacing the heart impose an emotional change? And what we found it was not so simple either, because it didn't by itself, cause the change it had to be in the right context. What we can take away from this is that to understand internal states, you have to consider the brain and the body together. You can't neglect the causal role that the body plays in setting the internal state of the brain.

Host: Shamini Bundell

That was Karl Deisseroth from Stanford University in the US. You also heard from Anna Beyeler from the French National Institute of Health and Medical Research in France. For more on that story, there'll be a link to the paper in the show notes and a link to Anna's News and Views article.

Host: Nick Petrić HoweComing up, since the DART spacecraft smashed into an asteroid, researchers have been busy analyzing all the data it produced. In just a moment, we'll be finding out what the data reveals. Right now though, it's time for the Research Highlights with Dan Fox.

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Dan Fox

The James Webb Space Telescope, or JWST, continues to expand our knowledge of the universe, sometimes even by accident, as it spots tiny unknown asteroids whilst still being calibrated. Researchers examining images of a 15-kilometer-wide object in the asteroid belt between Mars and Jupiter also spotted what looks like a much smaller asteroid less than 230 meters across. If the object can be confirmed with further observations, it will be one of the smallest objects ever seen in space, detected at a distance of more than 130 million kilometers. The author suggests that any images taken by JWST along the plane of the solar system will likely contain a few asteroids, and many of these will be new to science, with the solar system potentially containing hundreds of millions of small space rocks, which could be key to understanding its history. Don't wait to accidentally find that paper while you're looking for something else, read it in full in Astronomy and Astrophysics.

Researchers have measured the brain activity of a freely-moving octopus for the first time. Octopuses are among the most intelligent invertebrates on the planet, but catching a glimpse of the inner workings of their brains isn't easy. That's in no small part because the animals tend to remove any devices, like the ones that can measure brain activity that are attached to their bodies. But now, researchers have been able to surgically implant a recording device in an inner cavity below the skin. The devices then connect to electrodes placed in the animal's brains. The implants allowed the team to measure the brain activity of three octopuses for a full 12 hours, during which time the octopus has behaved normally, aside from exploring the incision site with their arms. The recording showed patterns that resembled mammalian brain activity as well as some that had not been previously reported. The researchers say this could provide an experimental platform for better understanding these creatures. Reach for that research over in Current Biology.

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Host: Nick Petrić Howe

In September last year, NASA's DART spacecraft, standing for Double Asteroid Redirection Test, smashed into the space rock, Dimorphos. The idea was to explore whether humanity could one day deflect potential planet killing asteroids. The test was a success. DART nudged Dimorphos orbit closer to the asteroid it rotates around. But just as important as the demonstration is the analysis that followed. What actually happened? And what's it mean for our ability to deflect asteroids? Well, now a suite of papers are being published in Nature, with all the maths and models that researchers have been making in the months since the impact. To find out more, I caught up with Alex Witze, who's been covering this story for Nature. Alex, hi.

Interviewee: Alex Witze

Hi.

Host: Nick Petrić Howe

Well, thank you so much for joining me, I'm interested to get into the ins and outs of the science that's coming out of the DART mission. So, the first thing to talk about is these papers, they've given us a bit of a better idea about the actual collision itself, so what can you tell me about what actually happened when the DART spacecraft hit Dimorphos?

Interviewee: Alex Witze

What these papers are showing us is kind of the gory final seconds and microseconds of what happens. Now, the whole point of this impact, of course, was to knock this asteroid a little bit off of its orbit around a larger asteroid and see if we could affect a space rock’s trajectory, the whole idea being can we protect ourselves from a dangerous asteroid in the future. And what we did was we threw the spacecraft at this asteroid, it came zooming in at more than six kilometers a second. So, just think how fast that is. And it just obliterated itself on the surface, and the papers are showing how it came flying in with its two solar panels kind of stretched out like bird wings, and how one of those bird wings clipped a giant boulder, and then the whole spacecraft body just smashed to bits on the surface.

Host: Nick Petrić Howe

So, the original thinking was this impact would shave around 10 to 15 minutes of how long it takes Dimorphos to orbit its partner, but it actually turned out that moved way more than this, around 33 minutes was shaved off. What have the analyses been saying about this? Do we know why this happened?

Interviewee: Alex Witze

Yeah, so it worked really, really well, this space crash worked much better than anybody had thought, or hoped it might possibly go, and there's a couple of reasons for that, and that's what these papers kind of really get into. One is that the asteroid is pretty rubbly. It's kind of just a whole bunch of little space rocks kind of not glued together very strongly by gravity, and so when DART hit it, it could pretty much fly apart, not the whole thing, the asteroid is still there, but a lot of it basically just pulverized, and it formed this big giant tail, which you could see in the sky for many weeks afterwards. So for one thing, Dimorphos was kind of smooshy, and then the second thing is that it just turned out to be super effective, the way in which the spacecraft imparted momentum to the asteroid and the way in which all this debris flying off the asteroid gave it even more momentum, even more oomph, kind of added up, to just really push it in its orbit much more strongly than people had thought.

Host: Nick Petrić Howe

And so, you said the sort of debris pushes the asteroid further, how does that work? How does debris coming off make it go further than we thought it would?

Interviewee: Alex Witze

Think of it like recoil almost, so if you like shot a shotgun into a surface and stuff came springing off, there is kind of a recoil effect in the opposite direction, so as the stuff sprays off, the object that you just hit kind of moves in the other direction. Remember, we're in space, we're kind of just going around in zero gravity, so things can be moved around very, very easily. I mean, even the pressure of sunlight can cause asteroids to change their orbit. So, if you like bang a little bit of stuff off the surface, the asteroid will start having an impulse in the opposite direction, and if you hit it really hard, if a lot of stuff comes flying off, it's almost like, this a bit of an exaggeration, but creating a little, you know, rocket thrust.

Host: Nick Petrić Howe

And you mentioned there stuff being kicked off, and we've talked about that sort of debris pushing it along, but it also, they call it ‘activated’ the asteroid, it made it into sort of look like a comet with a tail coming out. What's so interesting about this? There was a whole paper devoted to this.

Interviewee: Alex Witze

There's a whole class of objects in our solar system, a whole class of things that are called active asteroids, and they're kind of like this weird mix between asteroids and comets. So, asteroids you normally think of as it's just kind of a rock flying around the Sun doing it's like rocky thing, comets are more icy and they come sailing in from outside the solar system, and when they get closer to the sun, they start to vaporize, and they get these beautiful tails. So, you think of comets having these big, glorious tails in the sky, and asteroids are just points of light, so what the DART impact did was it basically made a comet out of an asteroid, loosely speaking, we don't have ice going on and stuff here, but by sort of creating one from scratch, it's helping scientists sort of understand a bit more about these objects, and they found a whole bunch more just in the last couple of years, again, they kind of look like a rock, but they have a tail. How does that happen? Where does that come from? So, by making one, by basically making a comet out of an asteroid, the DART impact is kind of helping scientists understand what is it take to have this giant tail flying off you if you're a space rock.

Host: Nick Petrić Howe

Oh, that's super cool. And then I guess the big question is, what does all of this data, what does all these analyses tell us about our ability to potentially deflect some asteroids in the future?

Interviewee: Alex Witze

So, the planetary defense folks, these are the people who have the job of saving the planet in the future if we've got some giant killer asteroid coming at us, the planetary defense folks are really excited about the results from the DART impact. So of course, this is one asteroid, one impact. If something were coming to get us, it's not going to be exactly like Dimorphos, but the fact that they've been able to send a spacecraft, do this impact, see this big change, gives them a lot more confidence that if we were to see some giant killer thing, or even a small not-so-killer, but we don't really want it hitting us thing, that we could send a spacecraft to it and have a bit more confidence that by slamming into it, we could deflect it off the trajectory to hit Earth. These are sort of science fiction scenarios that you hear about all the time, your Armageddon/Deep Impact movie stuff like that, but the NASA folks are super excited for what DART has shown, that we can actually do this. We've never shown that before, and now we've shown that we can do that.

Host: Nick Petrić Howe

And could we do this for any sort of asteroid? Or do we need to do more of these kinds of tests? Like what's the future for this?

Interviewee: Alex Witze

The future is really to sort of figure out how much do we need to know about an asteroid when it's coming at us. So, if once coming at us, and we can observe it enough, and we think it's a lot like Dimorphos, maybe we can be confident to just go ahead and throw something up there and try to deflect it. But, if something's coming at us, and we can't really tell what it is, maybe it's to faint, too far away, or whatever, maybe that means we would want to, like, really quickly build a spacecraft to go fly just check it out first, and then figure out what to do about it.

Host: Nick Petrić Howe

Alex Witze there. For more on this story, make sure you check out the show notes for a link to the news article.

Host: Shamini Bundell

That's all for this week. As always, you can keep in touch with us on Twitter, we're at @naturepodcast or you can send an email to podcast@nature.com. I'm Shamini Bundell.

Host: Nick Petrić Howe

And I'm Nick Petrić Howe, thanks for listening.