Ripples in rats’ brains tied to memory may also reduce sugar levels

Ripples of nerve cell activity that lock in memories may have an unexpected job outside of the brain: Dropping blood sugar levels in the body.

Just after a burst of ripples in a rat’s hippocampus, sugar levels elsewhere in the body dipped, new experiments show. The curveball results, published August 11 in Nature, suggest that certain types of brain activity and metabolism are entwined in surprising and mysterious ways.

“This paper represents a significant advance in our understanding of how the hippocampus modulates metabolism,” says Elizabeth Gould, a neuroscientist at Princeton University who wasn’t involved in the study.

Neural shudders called sharp-wave ripples zig and zag in the brains of people as they learn new things and draw memories back up (SN: 8/19/19). Ripples also feature prominently during deep sleep. Sleeping mammals, birds and even lizards known as Australian dragons have these bursts of electrical activity. Sharp-wave ripples are thought to accompany the neural work of transforming short-term knowledge into long-term memories.
Neuroscientist David Tingley wondered whether these signals might also change something outside of the brain. Working with neuroscientist György Buzsáki at New York University Grossman School of Medicine and colleagues, Tingley, now at Harvard University, fitted continuous glucose monitors onto the backs of rats. These devices, used by people with diabetes to keep tabs on sugar levels in the fluid around cells, provide a good proxy for blood sugar levels. The researchers simultaneously measured the rats’ brain waves with electrodes implanted in the hippocampus, a brain structure that plays a key role in memory.

Every so often, electrodes picked up clusters of ripples. About 10 minutes after a bout of ripples, sugar levels in the body fell, the glucose monitors showed. “We saw these dips in the second rat, and the third rat, and the fourth rat,” says Buzsáki. “It was super consistent. The magnitude is small but [the dips] are always there.”

To see if this connection between the ripples and the sugar dips was mere coincidence, the researchers forced nerve cells in the hippocampus to fire in response to light, creating artificial ripples. Sure enough, after a bout of these forced ripples, the rats’ sugar levels dropped.

What’s more, when the researchers jammed the ripples’ downstream signals with a drug that quiets nerve cells in a brain area called the lateral septum, sugar levels did not drop. That suggests these ripples send signals that ping-pong through the brain and ultimately tell the body to reduce its sugar.

“All of this was very surprising,” says Jan Born, a neuroscientist who studies metabolism at the University of Tübingen in Germany. You might expect a busy brain at work to call for more energy, in the form of sugar, not less, says Born, who cowrote a commentary on the new paper in the same issue of Nature. But here, “the brain says to the body, ‘We don’t need so much energy, so go down with your glucose levels.’ Why?” says Born, “It’s difficult to see its function.”

Buzsáki wonders whether these ripples might have evolved initially to aid in metabolism. “They were useful for the body first,” he speculates. As time passed, ripples may have been pulled in on other jobs, such as memory storage.

If this newfound link between brain waves and metabolism exists in people, it might suggest a way to influence sugar levels by tweaking ripples, Buzsáki says, an idea that might prove useful for people with diabetes or other metabolic problems. The hippocampus is deep in the brain, but its activity can be altered via magnetic or electrical jolts to easier-to-reach brain areas. Still, changing ripples for metabolic reasons is a far-off idea, Buzsáki cautions.

A blood test may help predict recovery from traumatic brain injury

Elevated blood levels of a specific protein may help scientists predict who has a better chance of bouncing back from a traumatic brain injury.

The protein, called neurofilament light or NfL for short, lends structural support to axons, the tendrils that send messages between brain cells. Levels of NfL peak on average at 10 times the typical level 20 days after injury and stay above normal a year later, researchers report September 29 in Science Translational Medicine. The higher the peak NfL blood concentrations after injury, the tougher the recovery for people with TBI six and 12 months later, shows the study of 197 people treated at eight trauma centers across Europe for moderate to severe TBI.

Brain scans of 146 participants revealed that their peak NfL concentrations predicted the extent of brain shrinkage after six months, and axon damage at six and 12 months after injury, neurologist Neil Graham of Imperial College London and his colleagues found.

These researchers also had a unique opportunity to check that the blood biomarker, which gives indirect clues about the brain injury, actually measured what was happening in the brain. In 18 of the participants that needed brain surgery, researchers sampled the fluid surrounding injured neurons. NfL concentrations there correlated with NfL concentrations in the blood.
“The work shows that a new ultrasensitive blood test can be used to accurately diagnose traumatic brain injury,” says Graham. “This blood test can predict quite precisely who’s going to make a good recovery and who’s going to have more difficulties.”

Study participants were adults and mostly male, so more work needs to be done to determine if these findings apply to women, children and people with mild TBI.

Finding a reliable biomarker for the severity and outlook of TBI, a head injury that disrupts brain function, could improve millions of lives. Studies of U.S. football players have brought attention to the injury (SN: 12/13/17), but it’s a far more widespread problem. Around 55 million people globally were living with a TBI in 2016, and there’s no one-size-fits-all treatment.

“No two traumatic brain injuries are alike,” says David Okonkwo, director of the Neurotrauma Clinical Trials Center at the University of Pittsburgh. Scientists have been looking for biomarkers of TBI injury such as NfL to develop injury-specific interventions, and Okonkwo says these new findings are promising for patients whose injury has damaged their axons.

“We have not had the tools to measure a specific injury type of an individual patient,” Okonkwo says. While this test probably is still a few years from use in U.S. clinics, other large research groups are looking for ways to use NfL and other blood-based biomarkers for diagnosing TBI and creating opportunities for intervention.

50 years ago, scientists were on the trail of ‘memory molecules’

The first memory molecule has been isolated, characterized and synthesized … [from the brains of] rats that had been shocked in the dark…. It is a protein and dubbed “scotophobin,” after the Greek words for “fear of the dark.” [One researcher] has injected synthetic rat scotophobin into the brains of hundreds of goldfish. While the fish indeed exhibited fear of the dark and resisted learning to swim into the dark, the fear was of brief duration.

Update
The idea that scotophobin stores memories and can be used to transfer them between organisms was met with intense skepticism and was eventually discredited by neuroscientists. But the search for a physical basis of memory continues. Over the last few decades, other memory molecule candidates have popped up, including a protein called PKM-zeta, which may help with memory retrieval, and even RNA (SN: 6/9/18, p. 9). Still, the dominant theory is that memories are stored in synapses, connections between nerve cells in the brain (SN: 2/3/18, p. 22).

The search for exomoons continues

David Kipping
Astronomer
Columbia University

After being featured in 2017, David Kipping and his colleagues formally reported in Science Advances the first detection of a potential exomoon — a moon orbiting a planet outside of the solar system. Signs of the Neptune-sized moon were spotted around a Jupiter-sized planet 8,000 light-years from Earth. Kipping has been hunting for more ever since, and has also become a hit on YouTube.

Have you found any more exomoons?
Well, I can’t really talk about that. We are close to releasing the results of a new survey of the ensemble of Jupiter-like planets discovered by the Kepler space telescope. Such planets are thought to be the best hunting ground for moons, being far from the gravitational influence of their star and large enough to support potentially massive moons. Unfortunately, the results are still not quite ready.

How have other scientists reacted?
The community is naturally skeptical. That was kind of the story of exoplanets. When researchers first discovered a hot Jupiter, no one believed it. It wasn’t until they discovered about 10 of them that people started to say that, actually, maybe these are real. I don’t know how it’s going to go with any exomoon candidate. Maybe what we’ve found is genuinely bogus, but I obviously hope not. We did our due diligence, and we’re very careful with the results.

It’s maybe not surprising that the first ones we find are going to be so large, because after all, they’re going to be the easiest to detect.… Actually, less than 1 percent of sunlike stars have hot Jupiters, but they dominated all of the first exoplanet detections just because they were so easy to find. Maybe the same thing will play out here.

In 2017, you had just launched a YouTube channel called Cool Worlds. How is that outreach going?
It’s been pretty overwhelming to us, because I’d never expected to get anywhere near the number of people watching who have watched. The last video [on what’s called the red sky paradox] got 200,000 views, and the one before it got 500,000. I mean, that’s just bonkers. I get e-mails from people, really amazing e-mails, that say how much the channel and the videos mean to them. That’s really incredible.

We have lots of people actually financially supporting us now. We give them special access to the videos and early access to the papers we’re writing. We hang out with some of them once every two months on a livestream and chat about science. It’s starting to be enough that I’m funding students through donations. I have this dream that I do research, it produces cool ideas, I talk about it on my outreach channel, people get excited about it and they support us, which enables me to do more research.

What are the greatest challenges you’ve faced since 2017?
I’m still [working to earn] tenure. It’s obviously one of the most stressful periods of your career because you don’t have that safety net yet that some young tenured colleagues enjoy. At the same time, you’re trying to raise a family and make sure you see your kids growing up. You don’t want to be a ghost at home. And so that’s been tricky, but [the pandemic] enabled me to spend a lot more time at home with the family.

— Interview by Cassie Martin

Research on wildfire smoke hits close to home

Emily Fischer
Atmospheric chemist
Colorado State University

Emily Fischer, featured in 2020, is in the midst of one of the most comprehensive analyses of wildfire smoke ever attempted. Since we last chatted with Fischer, her wildfire research and the way she talks about it have become more personal.

Have you started any projects since 2020?
We’re looking at the impact of smoke on the visible light range where photosynthesis occurs. There’s smoke blanketing the U.S. in summers now. Regardless of whether it’s at the ground, it’s somewhere in the atmosphere between the sun and the plants on the ground. In the Midwest, for example, over our corn and soybean belt, there’s smoke between a third to half of the days on average in July and August, during peak growing season. What does that mean for crops? How is that changing the light at the surface? If it’s boosting the diffuse fraction of radiation, and not decreasing the total radiation, that’s a boost to productivity.

Last year, you helped launch a national group called Science Moms. What is that?
We are a nonpartisan group of scientists who are also mothers. The goal of Science Moms is for us to speak directly [via a website, videos and events] on climate change to other mothers in ways that are accurate, digestible and also engaging. While roughly 60 percent of the U.S. population is worried about climate change, like 85 percent of moms are worried about climate change. But they don’t feel comfortable talking about it, or know how to talk to their representatives about it or even talk to their book club about it.

How have people responded to your outreach efforts?
I get all sorts of messages: “This is so different than any other climate communication that I’ve ever seen.” We’re trained as scientists to take the emotion out of things, but actually it’s very important for people to understand the feeling of climate change.

Last summer [2020], extreme fires impacted my own home. We had smoke here for multiple months, and my family ran from the Cameron Peak Fire.… For me, there was a shift from “These are the numbers, these are the graphs,” to “Oh, this is what my graphs feel like, this is what this trend feels like.”

Did your experience fleeing a wildfire shift your perspective around your science?
I’m the kind of person who studies what I see.… And so I should not have been surprised by that fire. I was out backpacking with my family, and it started one range over and my kids and I ran out, and we made it. So it was OK, but I was not sure it would be OK. When something like that happens to you, you have to respond to it. [Now] I think, when we calculate a change in something going forward, what does that mean? What are all the impacts that that could have?

Also, seeing the incident management teams working together to help people [during the fire] was very inspiring. I would say to my husband, “These teams are beautiful. They are functioning at such a high level under such hard conditions. If we could just harness this level of cooperation toward climate change action, or toward eliminating the pandemic, we [could] do anything.”

— Interview by Cassie Martin

A clever genetic tool tackles new troubles

Stanley Qi
Bioengineer
Stanford University

By disabling the DNA-cutting enzyme in the CRISPR system, Stanley Qi, featured in 2019, created a new and versatile tool. Attaching a range of molecules to these “dead Cas” enzymes has yielded an entire toolbox worth of DNA and RNA manipulators.

Is the strategy of disabling Cas molecules still popular among researchers?
I feel it’s getting more popular, for a number of reasons: One, people use … this tool to study how the genome works. Two, there are some new efforts using the tool to treat some genetic diseases. And three, there are some other exciting uses of this tool to think about other diseases, other topics that we can possibly tackle.

For example, this CRISPR system came from bacteria cells, right? They were used as weapons by the bacteria to fight against invading viruses. So we said, “OK, humans also have many foes like invading viruses. Can we repurpose this CRISPR to help us fight our infectious diseases?” That was the idea before the COVID-19 pandemic. We practiced first on influenza, seasonal flu…. We adapted a type of CRISPR system that targets a specific RNA molecule, and it works pretty well. I remember it working in January [2020] when the news started reporting, “Oh, there’s a new virus, it’s an RNA virus,” and we thought immediately, “What if we use this tool on this new RNA virus?”

Instead [of using the live virus], we used synthetic biology to mimic the RNA sequence.… [And we found] we can still very rapidly cleave and destroy this RNA virus and its fragments in the human lung cells. We were really excited. Since then we’ve been working very hard to follow up on the idea, to make this as fast as possible into a possible antiviral. We called it PAC-MAN.

Can you talk a bit about how the dead Cas, or dCas, approach has been improved and adapted?
One bigger use is for treating disease like a gene therapy. However, there’s still a number of features that have not been ideal for easy use or testing in clinics.… [For patient care,] people always think about making the system very, very compact and suitable into a nanoparticle or into a viral particle, so we can deliver them with ease into the human body. So that requires a miniaturization of the CRISPR system. And we actually did some work on that…. They are like two-thirds smaller than what people use.

And second is, many of these natural proteins from bacteria don’t work very well [in human cells].… So we did some protein engineering. Following these efforts, we actually created some highly compact, yet highly efficient dCas systems that can be easily delivered into the human body to turn on or off genes.

What are the greatest challenges you’ve faced in the last couple of years?
We are bioengineers and we think our strength is in creating stuff, modifying. Now as we step into the domain of applying these tools to solve real-world problems, the challenge is how to build a bridge between where we are to where we want to go. That usually requires learning a significant amount about a disease, about a new field, and thinking creatively on how to interface two fields.

— Interview by Ashley Braun

Astrophysicist writes about the stars for Spanish speakers

Paula Jofré
Astrophysicist
Universidad Diego Portales

Paula Jofré, featured in 2018, used the chemical composition of stars across the Milky Way like DNA to map the stars’ family tree. She recently filled in some details of the tree — and is filling a gap in the publishing world by writing a book about stars in Spanish.

What progress have you made on your stellar family tree?
In the first paper, the tree had three main branches. There was one that we could associate with a young thin disk, which is one of the populations in the Milky Way. Another was associated with an old, thick disk, which was the older component of the Milky Way. And then we had something in between…. Now, because we had more stars and more chemical elements and we made a better selection of which chemical elements to include, we could find that this strange population was actually an ancestor population of the thin disk. And one of the interpretations we had in the second paper [published in January in the Monthly Notices of the Royal Astronomical Society] was that they were produced all very quickly.

Other groups have found striking evidence of a galaxy that was merged into the Milky Way [billions of years ago]. And that [merging and mixing of gas] could have triggered what is called a star formation burst — lots of stars [forming] at the same time. So, it’s kind of exciting that we find in the tree a feature that could be attributed to a star formation burst … a few gigayears after the [merger of these two galaxies] that we know happened.

You’re also writing a popular book on stars. Can you tell me more about the book, Fósiles del cosmos: descifrando la historia de la Vía Láctea, or Fossils of the Cosmos: Deciphering the History of the Milky Way, and why you decided to write it?
It’s going to be published in November [in Chile]. It’s a book in Spanish for the public. I am teaching a class about stars in the Milky Way, a general astronomy class. And I’ve been finding that there is no proper literature in Spanish for the students.… The level is sometimes way too basic or too complex. So I wanted to write something for their level.

[The book] explains how stars create the chemical elements, what’s the role of Gaia [a satellite mission to map the galaxy], what’s the role of the Milky Way Mapper [another survey using Earth-based telescopes], about all these big surveys, why we care, what’s going on.

When I started writing it, of course, I started reading other books…. In all these general astronomy books, women are never highlighted. In my book, I have lots of quotes from 40 different women all around the world, working in my field.… I want to make the point that you can be a woman, you can be clever, you can dedicate yourself to something that is mentally challenging. You can be like any of these 40 women.

What’s the greatest challenge that you’ve faced since 2018?
The biggest challenge has been to promote hiring more women at the faculty level. Chile’s a very small country and they love new figures, young figures being highlighted by the United States. The moment I was in Science News,I became very popular [in Chile] very quickly. They needed the inspirational woman. And I kept saying, “I don’t want to be the only one. I want more women.”

I don’t know if you were aware of this collective Las Tesis; they made a dance for the social unrest that we had in Chile before the pandemic. It was a feminist movement that resonated for so many people in the world. The movement [says]: We want to be treated with respect, we want the same salary, we want the same opportunities, we want to feel safe on the streets.… But then, when you are fewer in academia, you’re not going to start jumping on the table and dancing, right? You have to argue … it’s difficult.

— Interview by Ashley Braun

Seeking solutions to climate change

Jeremy Freeman
Scientist and designer
CarbonPlan

When he was featured in 2016, Jeremy Freeman was developing new tools and methods to help scientists better analyze brain data. Now he is executive director of CarbonPlan, a nonprofit organization that he founded in March 2020 to tackle the climate crisis through open-source data and research.

You’ve shifted gears since 2016. Tell us about it.
I moved very far from neuroscience, and I’m now exclusively working on climate change. Our focus [at CarbonPlan] is the scientific integrity and transparency of climate solutions. [We do] a combination of research on different areas of climate science and strategies for addressing climate change. We [also] produce a variety of resources and tools for both the research community and the public at large.

Despite being a radically different field, there are some interesting commonalities, in terms of the value of having very accessible, open, publicly available data that speaks to critical issues. [For climate change,] issues around both what is changing in the climate and how we might address that, in different strategies we might take. Having as much of that information be developed in the open, in a way that others can contribute to, and making work available for others to read and evaluate and criticize and engage with — those are [also] values I felt really strongly about in the world of biomedical science.

What CarbonPlan work are you most proud of right now?
We have done a lot of analysis identifying very specific ways in which the implementation of forest carbon offset programs [the planting or preservation of trees to attempt to compensate for carbon emissions] haven’t worked. We did a comprehensive analysis of the role of forest carbon offsets in California’s cap-and-trade program, which is a massive sort of market of offsets on the order of $2 billion, and we identified about $400 million worth of offset credits that in our analysis do not reflect real climate benefits because of errors in how they were calculated with respect to issues that involve fundamental problems in statistics and ecology.

That team effort, led by Grayson Badgley and Danny Cullenward, along with a lot of other work that we’ve done on the role of offsets, is really starting to change the conversation, and wake people up to the fact that these approaches to dealing with climate change haven’t been working.

What other questions are you looking at?
There’s an area known as carbon removal, which refers to any mechanisms that draw down CO2 from the atmosphere. And carbon removal is really, really complicated, because there are a lot of different ways to potentially accomplish that.… So that’s an area where we’ve been very involved, studying, analyzing, comparing. We helped write, edit and produce a book called the CDR Primer — carbon dioxide removal primer. It’s, of course, a publicly available resource.

Have recent social justice movements influenced your work?
Absolutely.… Climate change is so fundamentally an issue of equity and an issue of justice. The burdens of climate change are going to be borne by those who were not directly responsible for it, and those who in many ways have been responsible for it will be more able to avoid its impacts. And there’s a deep injustice in that.… How to think about that is an important aspect of our work.… We’re interested in finding a way to be really complementary to a lot of existing community efforts around these issues.

— Interview by Aina Abell

Pluto’s dark side reveals clues to its atmosphere and frost cycles

Pluto’s dark side has come into dim view, thanks to the light of the dwarf planet’s moon.

When NASA’s New Horizons spacecraft flew past Pluto in 2015, almost all the images of the dwarf planet’s unexpectedly complex surface were of the side illuminated by the sun (SN: 7/15/15). Darkness shrouded the dwarf planet’s other hemisphere. Some of it, like the area near the south pole, hadn’t seen the sun for decades.

Now, mission scientists have finally released a grainy view of the dwarf planet’s dark side. The researchers describe the process to take the photo and what it tells them about how Pluto’s nitrogen cycle affects its atmosphere October 20 in the Planetary Science Journal.

Before New Horizons passed by Pluto, the team suspected the dwarf planet’s largest moon, Charon, might reflect enough light to illuminate the distant world’s surface. So the researchers had the spacecraft turn back toward the sun to take a parting peek at Pluto.
At first, the images just showed a ring of sunlight filtering through Pluto’s hazy atmosphere (SN: 7/24/15). “It’s very hard to see anything in that glare,” says planetary scientist John Spencer of the Southwest Research Institute in Boulder, Colo. “It’s like trying to read a street sign when you’re driving toward the setting sun and you have a dirty windshield.”

Spencer and colleagues took a few steps to make it possible to pull details of Pluto’s dark side out of the glare. First, the team had the spacecraft take 360 short snapshots of the backlit dwarf planet. Each was about 0.4 seconds long, to avoid overexposing the images. The team also took snapshots of the sun without Pluto in the frame so that the sun could be subtracted out after the fact.

Tod Lauer of the National Optical Astronomy Observatory in Tucson, Ariz., tried to process the images when he got the data in 2016. At the time, the rest of the data from New Horizons was still fresh and took up most of his attention, so he didn’t have the time to tackle such a tricky project.

But “it was something that just sat there and ate away at me,” Lauer says. He tried again in 2019. Because the spacecraft was moving as it took the images, each image was a little bit smeared or blurred. Lauer wrote a computer code to remove that blur from each individual frame. Then he added the reflected Charon light in each of those hundreds of images together to produce a single image.
“When Tod did that painstaking analysis, we finally saw something emerging in the dark there … giving us a little bit of a glimpse of what the dark pole of Pluto looks like,” Spencer says.

That the team got anything at all is impressive, says planetary scientist Carly Howett, also of the Southwest Research Institute and who is on the New Horizons team but was not involved in this work. “This dataset is really, really hard to work with,” she says. “Kudos to this team. I wouldn’t have wanted to do this.”

The image, Howett says, can help scientists understand how Pluto’s frigid nitrogen atmosphere varies with its decades-long seasons. Pluto’s atmosphere is controlled by how much nitrogen is in a gas phase in the air and how much is frozen on the surface. The more nitrogen ice that evaporates, the thicker the atmosphere becomes. If too much nitrogen freezes to the ground, the atmosphere could collapse altogether.
When New Horizons was there, Pluto’s south pole looked darker than the north pole. That suggests there was not a lot of fresh nitrogen frost freezing out of the atmosphere there, even though it was nearing winter. “The previous summer ended decades ago, but Pluto cools off pretty slowly,” Spencer says. “Maybe it’s still so warm [that] the frost can’t condense there, and that keeps the atmosphere from collapsing.”

There was a bright spot in the middle of the image, which could be a fresh ice deposit. That’s also not surprising, Howett says. The ices may still be moving from the north pole to the south pole as Pluto moves deeper into its wintertime.

“We’ve thought this for a long time. It makes sense,” she says. “But it’s nice to see it happening.”

Neutron star collisions probably make more gold than other cosmic smashups

The cosmic origins of elements heavier than iron are mysterious. One elemental birthplace came to light in 2017 when two neutron-rich dead stars collided and spewed out gold, platinum and other hefty elements (SN: 10/16/17). A few years later, a smashup of another neutron star and a black hole left scientists wondering which type of cosmic clash was the more prolific element foundry (SN: 6/29/21).

Now, they have an answer. Collisions of two neutron stars probably take the cake, scientists report October 25 in Astrophysical Journal Letters.

To create heavy elements after either type of collision, neutron star material must be flung into space, where a series of nuclear reactions called the r-process can transform the material (SN: 4/22/16).

How much material escapes into space, if any, depends on various factors. For example, in collisions of a neutron star and black hole, the black hole has to be relatively small, or “there’s no hope at all,” says astrophysicist Hsin-Yu Chen of MIT. “It’s going to swallow the neutron star right away,” without ejecting anything.

Questions remain about both types of collisions, spotted via the ripples in spacetime that they kick up. So Chen and colleagues considered a range of possibilities for the properties of neutron stars and black holes, such as the distributions of their masses and how fast they spin. The team then calculated the mass ejected by each type of collision under those varied conditions. In most scenarios, the neutron star–black hole mergers made a smaller quantity of heavy elements than the neutron star duos — in one case only about a hundredth the amount.

Still, the ultimate element factory ranking remains up in the air. The scientists compared just these two types of collisions, not other possible sources of heavy elements such as exploding stars (SN: 7/7/21).