Biology

sleeping-pills-stop-the-brain’s-system-for-cleaning-out-waste

Sleeping pills stop the brain’s system for cleaning out waste


Cleanup on aisle cerebellum

A specialized system sends pulses of pressure through the fluids in our brain.

Our bodies rely on their lymphatic system to drain excessive fluids and remove waste from tissues, feeding those back into the blood stream. It’s a complex yet efficient cleaning mechanism that works in every organ except the brain. “When cells are active, they produce waste metabolites, and this also happens in the brain. Since there are no lymphatic vessels in the brain, the question was what was it that cleaned the brain,” Natalie Hauglund, a neuroscientist at Oxford University who led a recent study on the brain-clearing mechanism, told Ars.

Earlier studies done mostly on mice discovered that the brain had a system that flushed its tissues with cerebrospinal fluid, which carried away waste products in a process called glymphatic clearance. “Scientists noticed that this only happened during sleep, but it was unknown what it was about sleep that initiated this cleaning process,” Hauglund explains.

Her study found the glymphatic clearance was mediated by a hormone called norepinephrine and happened almost exclusively during the NREM sleep phase. But it only worked when sleep was natural. Anesthesia and sleeping pills shut this process down nearly completely.

Taking it slowly

The glymphatic system in the brain was discovered back in 2013 by Dr. Maiken Nedergaard, a Danish neuroscientist and a coauthor of Hauglund’s paper. Since then, there have been numerous studies aimed at figuring out how it worked, but most of them had one problem: they were done on anesthetized mice.

“What makes anesthesia useful is that you can have a very controlled setting,” Hauglund says.

Most brain imaging techniques require a subject, an animal or a human, to be still. In mouse experiments, that meant immobilizing their heads so the research team could get clear scans. “But anesthesia also shuts down some of the mechanisms in the brain,” Hauglund argues.

So, her team designed a study to see how the brain-clearing mechanism works in mice that could move freely in their cages and sleep naturally whenever they felt like it. “It turned out that with the glymphatic system, we didn’t really see the full picture when we used anesthesia,” Hauglund says.

Looking into the brain of a mouse that runs around and wiggles during sleep, though, wasn’t easy. The team pulled it off by using a technique called flow fiber photometry which works by imaging fluids tagged with fluorescent markers using a probe implanted in the brain. So, the mice got the optical fibers implanted in their brains. Once that was done, the team put fluorescent tags in the mice’s blood, cerebrospinal fluid, and on the norepinephrine hormone. “Fluorescent molecules in the cerebrospinal fluid had one wavelength, blood had another wavelength, and norepinephrine had yet another wavelength,” Hauglund says.

This way, her team could get a fairly precise idea about the brain fluid dynamics when mice were awake and asleep. And it turned out that the glymphatic system basically turned brain tissues into a slowly moving pump.

Pumping up

“Norepinephrine is released from a small area of the brain in the brain stem,” Hauglund says. “It is mainly known as a response to stressful situations. For example, in fight or flight scenarios, you see norepinephrine levels increasing.” Its main effect is causing blood vessels to contract. Still, in more recent research, people found out that during sleep, norepinephrine is released in slow waves that roll over the brain roughly once a minute. This oscillatory norepinephrine release proved crucial to the operation of the glymphatic system.

“When we used the flow fiber photometry method to look into the brains of mice, we saw these slow waves of norepinephrine, but we also saw how it works in synchrony with fluctuation in the blood volume,” Hauglund says.

Every time the norepinephrine level went up, it caused the contraction of the blood vessels in the brain, and the blood volume went down. At the same time, the contraction increased the volume of the perivascular spaces around the blood vessels, which were immediately filled with the cerebrospinal fluid.

When the norepinephrine level went down, the process worked in reverse: the blood vessels dilated, letting the blood in and pushing the cerebrospinal fluid out. “What we found was that norepinephrine worked a little bit like a conductor of an orchestra and makes the blood and cerebrospinal fluid move in synchrony in these slow waves,” Hauglund says.

And because the study was designed to monitor this process in freely moving, undisturbed mice, the team learned exactly when all this was going on. When mice were awake, the norepinephrine levels were much higher but relatively steady. The team observed the opposite during the REM sleep phase, where the norepinephrine levels were consistently low. The oscillatory behavior was present exclusively during the NREM sleep phase.

So, the team wanted to check how the glymphatic clearance would work when they gave the mice zolpidem, a sleeping drug that had been proven to increase NREM sleep time. In theory, zolpidem should have boosted brain-clearing. But it turned it off instead.

Non-sleeping pills

“When we looked at the mice after giving them zolpidem, we saw they all fell asleep very quickly. That was expected—we take zolpidem because it makes it easier for us to sleep,” Hauglund says. “But then we saw those slow fluctuations in norepinephrine, blood volume, and cerebrospinal fluid almost completely stopped.”

No fluctuations meant the glymphatic system didn’t remove any waste. This was a serious issue, because one of the cellular waste products it is supposed to remove is amyloid beta, found in the brains of patients suffering from Alzheimer’s disease.

Hauglund speculates it could be possible zolpidem induces a state very similar to sleep but at the same time it shuts down important processes that happen during sleep. While heavy zolpidem use has been associated with increased risk of the Alzheimer disease, it is not clear if this increased risk was there because the drug was inhibiting oscillatory norepinephrine release in the brain. To better understand this, Hauglund wants to get a closer look into how the glymphatic system works in humans.

“We know we have the same wave-like fluid dynamics in the brain, so this could also drive the brain clearance in humans,” Haugland told Ars. “Still, it’s very hard to look at norepinephrine in the human brain because we need an invasive technique to get to the tissue.”

But she said norepinephrine levels in people can be estimated based on indirect clues. One of them is pupil dilation and contraction, which work in in synchrony with the norepinephrine levels. Another other clue may lay in microarousals—very brief, imperceivable awakenings which, Hauglund thinks, can be correlated with the brain clearing mechanism. “I am currently interested in this phenomenon […]. Right now we have no idea why microarousals are there or what function they have” Hauglund says.

But the last step she has on her roadmap is making better sleeping pills. “We need sleeping drugs that don’t have this inhibitory effect on the norepinephrine waves. If we can have a sleeping pill that helps people sleep without disrupting their sleep at the same time it will be very important,” Hauglund concludes.

Cell, 2025. DOI: 10.1016/j.cell.2024.11.027

Photo of Jacek Krywko

Jacek Krywko is a freelance science and technology writer who covers space exploration, artificial intelligence research, computer science, and all sorts of engineering wizardry.

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Peeing is contagious among chimps

Those results supported the initial hypothesis that chimps tended to urinate in sync rather than randomly. Further analysis showed that the closer a chimp was to another peeing chimp, the more likely the probability of that chimp peeing as well—evidence of social contagion. Finally, Onishi et al. wanted to explore whether social relationships (like socially close pairs, evidenced by mutual grooming and similar behaviors) influenced contagious urination. The only social factor that proved relevant was dominance, with less-dominant chimps being more prone to contagious urination.

There may still be other factors influencing the behavior, and more experimental research is needed on potential sensory cues and social triggers in order to identify possible underlying mechanisms for the phenomenon. Furthermore, this study was conducted with a captive chimp population; to better understand potential evolutionary roots, there should be research on wild chimp populations, looking at possible links between contagious urination and factors like ranging patterns, territory use, and so forth.

“This was an unexpected and fascinating result, as it opens up multiple possibilities for interpretation,” said coauthor Shinya Yamamoto, also of Kyoto University. “For instance, it could reflect hidden leadership in synchronizing group activities, the reinforcement of social bonds, or attention bias among lower-ranking individuals. These findings raise intriguing questions about the social functions of this behavior.”

DOI: Current Biology, 2025. 10.1016/j.cub.2024.11.052 (About DOIs).

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Life is thriving in the subsurface depths of Earth

Nitrospirota is an archaeal phylum that’s particularly common in the terrestrial subsurface. Some species of nitrospirota are capable of oxidizing ammonia, while others can reduce it to nitrite, which is used by phytoplankton and also defends against pathogens in the human stomach, mouth, and skin.

Proteobacteria is a bacterial phylum that’s especially abundant in the terrestrial and marine subsurface. Some proteobacteria live in deep ocean trenches, and oxidize carbon monoxide (which contributes to global warming and depletes ozone). Bacteria also common in the marine subsurface include Desulfobacteria and Methylomirabilota. Desulfobacteria reduce sulfates, and other sulfate-reducing bacterias have already shown they can be used to help clean up contaminated soil. Methylomirabilota help control methane levels in the atmosphere by oxidizing methane.

Something unexpected that caught Ruff’s attention was how total diversity went up with depth. This was surprising because less energy is available at deeper levels of the subsurface. For archaea, diversity went up with the increase in depth in terrestrial environments but not marine environments. The same happened with bacteria, except in marine instead of terrestrial environments.

Much of what lies far below our feet still eludes us. Ruff suggests that single-cell microbes in even deeper, yet unexplored levels of the subsurface may have adapted to the absence of energy by slowing down their metabolisms so drastically that it could take decades, even centuries, for them to divide just once.

If there really are microbes that manage to live longer than humans with this survival tactic, it is possible similar species might be hiding on planets such as Mars, where the surface has long been blasted by radiation.

“Understanding deep life on Earth could be a model for discovering if there was life on Mars, and if it has survived,” Ruff said in a press release.

Maybe future technology could retrieve samples several kilometers below the Martian surface. Until then, keep digging.

Science Advances, 2024. DOI: 10.1126/sciadv.adq0645

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US to start nationwide testing for H5N1 flu virus in milk supply

So, the ultimate goal of the USDA is to eliminate cattle as a reservoir. When the Agency announced it was planning for this program, it noted that there were two candidate vaccines in trials. Until those are validated, it plans to use the standard playbook for handling emerging infections: contact tracing and isolation. And it has the ability to compel cattle and their owners to be more cooperative than the human population turned out to be.

The five-step plan

The USDA refers to isolation and contact tracing as Stage 3 of a five-stage plan for controlling H5N1 in cattle, with the two earlier stages being the mandatory sampling and testing, meant to be handled on a state-by-state basis. Following the successful containment of the virus in a state, the USDA will move on to batch sampling to ensure each state remains virus-free. This is essential, given that we don’t have a clear picture of how many times the virus has jumped from its normal reservoir in birds into the cattle population.

That makes it possible that reaching Stage 5, which the USDA terms “Demonstrating Freedom from H5 in US Dairy Cattle,” will turn out to be impossible. Dairy cattle are likely to have daily contact with birds, and it may be that the virus will be regularly re-introduced into the population, leaving containment as the only option until the vaccines are ready.

Testing will initially focus primarily on states where cattle-to-human transmission is known to have occurred or the virus is known to be present: California, Colorado, Michigan, Mississippi, Oregon, and Pennsylvania. If you wish to track the progress of the USDA’s efforts, it will be posting weekly updates.

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Lizards and snakes are 35 million years older than we thought

Lizards are ancient creatures. They were around before the dinosaurs and persisted long after dinosaurs went extinct. We’ve now found they are 35 million years older than we thought they were.

Cryptovaranoides microlanius was a tiny lizard that skittered around what is now southern England during the late Triassic, around 205 million years ago. It likely snapped up insects in its razor teeth (its name means “hidden lizard, small butcher”). But it wasn’t always considered a lizard. Previously, a group of researchers who studied the first fossil of the creature, or holotype, concluded that it was an archosaur, part of a group that includes the extinct dinosaurs and pterosaurs along with extant crocodilians and birds.

Now, another research team from the University of Bristol has analyzed that fossil and determined that Cryptovaranoides is not an archosaur but a lepidosaur, part of a larger order of reptiles that includes squamates, the reptile group that encompasses modern snakes and lizards. It is now also the oldest known squamate.

The misunderstandings about this species all come down to features in its bones that are squamate apomorphies. These are traits unique to squamates that were not present in their ancestral form, but evolved later. Certain forelimb bones, skull bones, jawbones, and even teeth of Cryptovaranoides share characteristics with those from both modern and extinct lizards.

Wait, what is that thing?

So what does the new team argue that the previous team that studied Cryptovaranoides gets wrong? The new paper argues that the interpretation of a few bones in particular stand out, especially the humerus and radius.

In the humerus of this lizard, structures called the ectepicondylar and entepicondylar foramina, along with the radial condyle, were either not considered or may have been misinterpreted. The entepicondylar foramen is an opening in the far end of the humerus, which is an upper arm bone in humans and upper forelimb bone in lizards. The ectepicondylar foramen is a structure on the outer side of the humerus where the extensor muscles attach, helping a lizard bend and straighten its legs. Both features are “often regarded as key lepidosaur and squamate characteristics,” the Bristol research team said in a study recently published in Royal Society Open Science.

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Researchers finally identify the ocean’s “mystery mollusk”

Some of the most bizarre lifeforms on Earth lurk in the deeper realms of the ocean. There was so little known about one of these creatures that it took 20 years just to figure out what exactly it was. Things only got weirder from there.

The organism’s distinctive, glowing presence was observed by multiple deep-sea missions between 2000 to 2021 but was simply referred to as “mystery mollusk.” A team of Monterey Bay Aquarium Research Institute (MBARI) researchers has now reviewed extensive footage of past mystery mollusk sightings and used MBARI’s remotely operated vehicles (ROVs) to observe it and collect samples. They’ve given it a name and have finally confirmed that it is a nudibranch—the first and only nudibranch known to live at such depths.

Bathydevius caudactylus, as this nudibranch is now called, lives 1,000–4,000 meters (3,300–13,100 feet) deep in the ocean’s bathypelagic or midnight zone. It moves like a jellyfish, eats like a Venus flytrap, and is bioluminescent, and its genes are distinct enough for it to be classified as the first member of a new phylogenetic family.

“Anatomy, diet, behavior, bioluminescence, and habitat distinguish this surprising nudibranch from all previously described species, and genetic evidence supports its placement in a new family,” the MBARI research team said in a study recently published in Deep Sea Research. 

Is that a…?

Nudibranchs are gastropods, which literally translates to “stomach foot” since the “foot” they crawl around on when not swimming is right below their guts. They are part of a larger group that includes terrestrial and aquatic snails and slugs. B. caudactylus, however, seems to get around more like a jellyfish than a sea slug. It mostly swims using an oral hood that opens and closes to propel itself backward through the water in a manner similar to many jellyfish.

The hood of B. caudactylus can also act something like a Venus flytrap. While it is not a hinged structure like the leaves of the plant, it is used to trap prey. Typically small crustaceans, the prey are then pushed to the mouth at the back of the hood.

The mystery mollusk.

The nudibranch also seems to have a unique way of avoiding becoming food itself. Projections at the end of its tail, known as dactyls, can detach if needed, much like the tails of some lizard species. The MBARI team thinks that these dactyls are possibly a lure meant to trick predators while the nudibranch swims away. They later regenerate.

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How should we treat beings that might be sentient?


Being aware of the maybe self-aware

A book argues that we’ve not thought enough about things that might think.

What rights should a creature with ambiguous self-awareness, like an octopus, be granted. Credit: A. Martin UW Photography

If you aren’t yet worried about the multitude of ways you inadvertently inflict suffering onto other living creatures, you will be after reading The Edge of Sentience by Jonathan Birch. And for good reason. Birch, a Professor of Philosophy at the London College of Economics and Political Science, was one of a team of experts chosen by the UK government to establish the Animal Welfare Act (or Sentience Act) in 2022—a law that protects animals whose sentience status is unclear.

According to Birch, even insects may possess sentience, which he defines as the capacity to have valenced experiences, or experiences that feel good or bad. At the very least, Birch explains, insects (as well as all vertebrates and a selection of invertebrates) are sentience candidates: animals that may be conscious and, until proven otherwise, should be regarded as such.

Although it might be a stretch to wrap our mammalian minds around insect sentience, it is not difficult to imagine that fellow vertebrates have the capacity to experience life, nor does it come as a surprise that even some invertebrates, such as octopuses and other cephalopod mollusks (squid, cuttlefish, and nautilus) qualify for sentience candidature. In fact, one species of octopus, Octopus vulgaris, has been protected by the UK’s Animal Scientific Procedures Act (ASPA) since 1986, which illustrates how long we have been aware of the possibility that invertebrates might be capable of experiencing valenced states of awareness, such as contentment, fear, pleasure, and pain.

A framework for fence-sitters

Non-human animals, of course, are not the only beings with an ambiguous sentience stature that poses complicated questions. Birch discusses people with disorders of consciousness, embryos and fetuses, neural organoids (brain tissue grown in a dish), and even “AI technologies that reproduce brain functions and/or mimic human behavior,” all of which share the unenviable position of being perched on the edge of sentience—a place where it is excruciatingly unclear whether or not these individuals are capable of conscious experience.

What’s needed, Birch argues, when faced with such staggering uncertainty about the sentience stature of other beings, is a precautionary framework that outlines best practices for decision-making regarding their care. And in The Edge of Sentience, he provides exactly that, in meticulous, orderly detail.

Over more than 300 pages, he outlines three fundamental framework principles and 26 specific case proposals about how to handle complex situations related to the care and treatment of sentience-edgers. For example, Proposal 2 cautions that “a patient with a prolonged disorder of consciousness should not be assumed incapable of experience” and suggests that medical decisions made on their behalf cautiously presume they are capable of feeling pain. Proposal 16 warns about conflating brain size, intelligence, and sentience, and recommends decoupling the three so that we do not incorrectly assume that small-brained animals are incapable of conscious experience.

Surgeries and stem cells

Be forewarned, some topics in The Edge of Sentience are difficult. For example, Chapter 10 covers embryos and fetuses. In the 1980s, Birch shares, it was common practice to not use anesthesia on newborn babies or fetuses when performing surgery. Why? Because whether or not newborns and fetuses experience pain was up for debate. Rather than put newborns and fetuses through the risks associated with anesthesia, it was accepted practice to give them a paralytic (which prevents all movement) and carry on with invasive procedures, up to and including heart surgery.

After parents raised alarms over the devastating outcomes of this practice, such as infant mortality, it was eventually changed. Birch’s takeaway message is clear: When in doubt about the sentience stature of a living being, we should probably assume it is capable of experiencing pain and take all necessary precautions to prevent it from suffering. To presume the opposite can be unethical.

This guidance is repeated throughout the book. Neural organoids, discussed in Chapter 11, are mini-models of brains developed from stem cells. The potential for scientists to use neural organoids to unravel the mechanisms of debilitating neurological conditions—and to avoid invasive animal research while doing so—is immense. It is also ethical, Birch posits, since studying organoids lessens the suffering of research animals. However, we don’t yet know whether or not neural tissue grown in a dish has the potential to develop sentience, so he argues that we need to develop a precautionary approach that balances the benefits of reduced animal research against the risk that neural organoids are capable of being sentient.

A four-pronged test

Along this same line, Birch says, all welfare decisions regarding sentience-edgers require an assessment of proportionality. We must balance the nature of a given proposed risk to a sentience candidate with potential harms that could result if nothing is done to minimize the risk. To do this, he suggests testing four criteria: permissibility-in-principle, adequacy, reasonable necessity, and consistency. Birch refers to this assessment process as PARC, and deep dives into its implementation in chapter eight.

When applying the PARC criteria, one begins by testing permissibility-in-principle: whether or not the proposed response to a risk is ethically permissible. To illustrate this, Birch poses a hypothetical question: would it be ethically permissible to mandate vaccination in response to a pandemic? If a panel of citizens were in charge of answering this question, they might say “no,” because forcing people to be vaccinated feels unethical. Yet, when faced with the same question, a panel of experts might say “yes,” because allowing people to die who could be saved by vaccination also feels unethical. Gauging permissibility-in-principle, therefore, entails careful consideration of the likely possible outcomes of a proposed response. If an outcome is deemed ethical, it is permissible.

Next, the adequacy of a proposed response must be tested. A proportionate response to a risk must do enough to lessen the risk. This means the risk must be reduced to “an acceptable level” or, if that’s not possible, a response should “deliver the best level of risk reduction that can be achieved” via an ethically permissible option.

The third test is reasonable necessity. A proposed response to a risk must not overshoot—it should not go beyond what is reasonably necessary to reduce risk, in terms of either cost or imposed harm. And last, consistency should be considered. The example Birch presents is animal welfare policy. He suggests we should always “aim for taxonomic consistency: our treatment of one group of animals (e.g., vertebrates) should be consistent with our treatment of another (e.g., invertebrates).”

The Edge of Sentience, as a whole, is a dense text overflowing with philosophical rhetoric. Yet this rhetoric plays a crucial role in the storytelling: it is the backbone for Birch’s clear and organized conclusions, and it serves as a jumping-off point for the logical progression of his arguments. Much like “I think, therefore I am” gave René Descartes a foundation upon which to build his idea of substance dualism, Birch uses the fundamental position that humans should not inflict gratuitous suffering onto fellow creatures as a base upon which to build his precautionary framework.

For curious readers who would prefer not to wade too deeply into meaty philosophical concepts, Birch generously provides a shortcut to his conclusions: a cheat sheet of his framework principles and special case proposals is presented at the front of the book.

Birch’s ultimate message in The Edge of Sentience is that a massive shift in how we view beings with a questionable sentience status should be made. And we should ideally make this change now, rather than waiting for scientific research to infallibly determine who and what is sentient. Birch argues that one way that citizens and policy-makers can begin this process is by adopting the following decision-making framework: always avoid inflicting gratuitous suffering on sentience candidates; take precautions when making decisions regarding a sentience candidate; and make proportional decisions about the care of sentience candidates that are “informed, democratic and inclusive.”

You might be tempted to shake your head at Birch’s confidence in humanity. No matter how deeply you agree with his stance of doing no harm, it’s hard to have confidence in humanity given our track record of not making big changes for the benefit of living creatures, even when said creatures includes our own species (cue in global warming here). It seems excruciatingly unlikely that the entire world will adopt Birch’s rational, thoughtful, comprehensive plan for reducing the suffering of all potentially sentient creatures. Yet Birch, a philosopher at heart, ignores human history and maintains a tone of articulate, patient optimism. He clearly believes in us—he knows we can do better—and he offers to hold our hands and walk us through the steps to do so.

Lindsey Laughlin is a science writer and freelance journalist who lives in Portland, Oregon, with her husband and four children. She earned her BS from UC Davis with majors in physics, neuroscience, and philosophy.

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tweaking-non-neural-brain-cells-can-cause-memories-to-fade

Tweaking non-neural brain cells can cause memories to fade


Neurons and a second cell type called an astrocyte collaborate to hold memories.

Astrocytes (labelled in black) sit within a field of neurons. Credit: Ed Reschke

“If we go back to the early 1900s, this is when the idea was first proposed that memories are physically stored in some location within the brain,” says Michael R. Williamson, a researcher at the Baylor College of Medicine in Houston. For a long time, neuroscientists thought that the storage of memory in the brain was the job of engrams, ensembles of neurons that activate during a learning event. But it turned out this wasn’t the whole picture.

Williamson’s research investigated the role astrocytes, non-neuron brain cells, play in the read-and-write operations that go on in our heads. “Over the last 20 years the role of astrocytes has been understood better. We’ve learned that they can activate neurons. The addition we have made to that is showing that there are subsets of astrocytes that are active and involved in storing specific memories,” Williamson says in describing a new study his lab has published.

One consequence of this finding: Astrocytes could be artificially manipulated to suppress or enhance a specific memory, leaving all other memories intact.

Marking star cells

Astrocytes, otherwise known as star cells due to their shape, play various roles in the brain, and many are focused on the health and activity of their neighboring neurons. Williamson’s team started by developing techniques that enabled them to mark chosen ensembles of astrocytes to see when they activate genes (including one named c-Fos) that help neurons reconfigure their connections and are deemed crucial for memory formation. This was based on the idea that the same pathway would be active in neurons and astrocytes.

“In simple terms, we use genetic tools that allow us to inject mice with a drug that artificially makes astrocytes express some other gene or protein of interest when they become active,” says Wookbong Kwon, a biotechnologist at Baylor College and co-author of the study.

Those proteins of interest were mainly fluorescent proteins that make cells fluoresce bright red. This way, the team could spot the astrocytes in mouse brains that became active during learning scenarios. Once the tagging system was in place, Williamson and his colleagues gave their mice a little scare.

“It’s called fear conditioning, and it’s a really simple idea. You take a mouse, put it into a new box, one it’s never seen before. While the mouse explores this new box, we just apply a series of electrical shocks through the floor,” Williamson explains. A mouse treated this way remembers this as an unpleasant experience and associates it with contextual cues like the box’s appearance, the smells and sounds present, and so on.

The tagging system lit up all astrocytes that expressed the c-Fos gene in response to fear conditioning. Williamson’s team inferred that this is where the memory is stored in the mouse’s brain. Knowing that, they could move on to the next question, which was if and how astrocytes and engram neurons interacted during this process.

Modulating engram neurons

“Astrocytes are really bushy,” Williamson says. They have a complex morphology with lots and lots of micro or nanoscale processes that infiltrate the area surrounding them. A single astrocyte can contact roughly 100,000 synapses, and not all of them will be involved in learning events. So the team looked for correlations between astrocytes activated during memory formation and the neurons that were tagged at the same time.

“When we did that, we saw that engram neurons tended to be contacting the astrocytes that are active during the formation of the same memory,” Williamson says. To see how astrocytes’ activity affects neurons, the team artificially stimulated the astrocytes by microinjecting them with a virus engineered to induce the expression of the c-Fos gene. “It directly increased the activity of engram neurons but did not increase the activity of non-engram neurons in contact with the same astrocyte,” Williamson explains.

This way his team established that at least some astrocytes could preferentially communicate with engram neurons. The researchers also noticed that astrocytes involved in memorizing the fear conditioning event had elevated levels of a protein called NFIA, which is known to regulate memory circuits in the hippocampus.

But probably the most striking discovery came when the researchers tested whether the astrocytes involved in memorizing an event also played a role in recalling it later.

Selectively forgetting

The first test to see if astrocytes were involved in recall was to artificially activate them when the mice were in a box that they were not conditioned to fear. It turned out artificial activation of astrocytes that were active during the formation of a fear memory formed in one box caused the mice to freeze even when they were in a different one.

So, the next question was, if you just killed or otherwise disabled an astrocyte ensemble active during a specific memory formation, would it just delete this memory from the brain? To get that done, the team used their genetic tools to selectively delete the NFIA protein in astrocytes that were active when the mice received their electric shocks. “We found that mice froze a lot less when we put them in the boxes they were conditioned to fear. They could not remember. But other memories were intact,” Kwon claims.

The memory was not completely deleted, though. The mice still froze in the boxes they were supposed to freeze in, but they did it for a much shorter time on average. “It looked like their memory was maybe a bit foggy. They were not sure if they were in the right place,” Williamson says.

After figuring out how to suppress a memory, the team also figured out where the “undo” button was and brought it back to normal.

“When we deleted the NFIA protein in astrocytes, the memory was impaired, but the engram neurons were intact. So, the memory was still somewhere there. The mice just couldn’t access it,” Williamson claims. The team brought the memory back by artificially stimulating the engram neurons using the same technique they employed for activating chosen astrocytes. “That caused the neurons involved in this memory trace to be activated for a few hours. This artificial activity allowed the mice to remember it again,” Williamson says.

The team’s vision is that in the distant future this technique can be used in treatments targeting neurons that are overactive in disorders such as PTSD. “We now have a new cellular target that we can evaluate and potentially develop treatments that target the astrocyte component associated with memory,” Williamson claims. But there’s lot more to learn before anything like that becomes possible. “We don’t yet know what signal is released by an astrocyte that acts on the neuron. Another thing is our study was focused on one brain region, which was the hippocampus, but we know that engrams exist throughout the brain in lots of different regions. The next step is to see if astrocytes play the same role in other brain regions that are also critical for memory,” Williamson says.

Nature, 2024.  DOI: 10.1038/s41586-024-08170-w

Photo of Jacek Krywko

Jacek Krywko is a freelance science and technology writer who covers space exploration, artificial intelligence research, computer science, and all sorts of engineering wizardry.

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This elephant figured out how to use a hose to shower

And the hose-showering behavior was “lateralized,” that is, Mary preferred targeting her left body side more than her right. (Yes, Mary is a “left-trunker.”) Mary even adapted her showering behavior depending on the diameter of the hose: she preferred showering with a 24-mm hose over a 13-mm hose and preferred to use her trunk to shower rather than a 32-mm hose.

It’s not known where Mary learned to use a hose, but the authors suggest that elephants might have an intuitive understanding of how hoses work because of the similarity to their trunks. “Bathing and spraying themselves with water, mud, or dust are very common behaviors in elephants and important for body temperature regulation as well as skin care,” they wrote. “Mary’s behavior fits with other instances of tool use in elephants related to body care.”

Perhaps even more intriguing was Anchali’s behavior. While Anchali did not use the hose to shower, she nonetheless exhibited complex behavior in manipulating the hose: lifting it, kinking the hose, regrasping the kink, and compressing the kink. The latter, in particular, often resulted in reduced water flow while Mary was showering. Anchali eventually figured out how to further disrupt the water flow by placing her trunk on the hose and lowering her body onto it. Control experiments were inconclusive about whether Anchali was deliberately sabotaging Mary’s shower; the two elephants had been at odds and behaved aggressively toward each other at shower times. But similar cognitively complex behavior has been observed in elephants.

“When Anchali came up with a second behavior that disrupted water flow to Mary, I became pretty convinced that she is trying to sabotage Mary,” Brecht said. “Do elephants play tricks on each other in the wild? When I saw Anchali’s kink and clamp for the first time, I broke out in laughter. So, I wonder, does Anchali also think this is funny, or is she just being mean?

Current Biology, 2024. DOI: 10.1016/j.cub.2024.10.017  (About DOIs).

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fungi-may-not-think,-but-they-can-communicate

Fungi may not think, but they can communicate

Because the soil layer was so thin, most hyphae, which usually grow and spread underground by releasing spores, were easily seen, giving the researchers an opportunity to observe where connections were being made in the mycelium. Early hyphal coverage was not too different between the X and circle formations. Later, each showed a strong hyphal network, which makes up the mycelium, but there were differences between them.

While the hyphal network was pretty evenly distributed around the circle, there were differences between the inner and outer blocks in the X arrangement. Levels of decay activity were determined by weighing the blocks before and after the incubation period, and decay was pretty even throughout the circle, but especially evident on the four outermost blocks of the X. The researchers suggest that there were more hyphal connections on those blocks for a reason.

“The outermost four blocks, which had a greater degree of connection, may have served as “outposts” for foraging and absorbing water and nutrients from the soil, facilitated by their greater hyphal connections,” they said in the same study.

Talk to me

Fungal mycelium experiences what’s called acropetal growth, meaning it grows outward in all directions from the center. Consistent with this, the hyphae started out growing outward from each block. But over time, the hyphae shifted to growing in the direction that would get them the most nutrients.

Why did it change? Here is where the team thinks communication comes in. Previous studies found electrical signals are transmitted through hyphae. These signals sync up after the hyphae connect into one huge mycelium, much like the signals transmitted among neurons in organisms with brains. Materials such as nutrients are also transferred throughout the network.

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bats-use-echolocation-to-make-mental-maps-for-navigation

Bats use echolocation to make mental maps for navigation

Bat maps

To evaluate the route each bat took to get back to the roost, the team used their simulations to measure the echoic entropy it experienced along the way. The field where the bats were released was a low echoic entropy area, so during those first few minutes when they were flying around they were likely just looking for some more distinct, higher entropy landmarks to figure out where they were. Once they were oriented, they started flying to the roost, but not in a straight line. They meandered a bit, and the groups with higher sensory deprivation tended to meander more.

The meandering, researchers suspect, was due to trouble the bats had with maintaining the steady path relying on echolocation alone. When they were detecting distinctive landmarks like a specific orchard, they corrected the course. Repeating the process eventually brought them to their roost.

But could this be landmark-based navigation? Or perhaps simple beaconing, where an animal locks onto something like a distant light and moves toward it?

The researchers argue in favor of cognitive acoustic maps. “I think if echolocation wasn’t such a limited sensory modality, we couldn’t reach a conclusion about the bats using cognitive acoustic maps,” Goldshtein says. The distance between landmarks the bats used to correct their flight path was significantly longer than echolocation’s sensing range. Yet they knew which direction the roost was relative to one landmark, even when the next landmark on the way was acoustically invisible. You can’t do that without having the area mapped.

“It would be really interesting to understand how other bats do that, to compare between species,” Goldshtein says. There are bats that fly over a thousand meters above the ground, so they simply can’t sense any landmarks using echolocation. Other species hunt over sea, which, as per this team’s simulations, would be just one huge low-entropy area. “We are just starting. That’s why I do not study only navigation but also housing, foraging, and other aspects of their behavior. I think we still don’t know enough about bats in general,” Goldshtein claims.

Science, 2024.  DOI: 10.1126/science.adn6269

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these-hornets-break-down-alcohol-so-fast-that-they-can’t-get-drunk

These hornets break down alcohol so fast that they can’t get drunk

Many animals, including humans, have developed a taste for alcohol in some form, but excessive consumption often leads to adverse health effects. One exception is the Oriental wasp. According to a new paper published in the Proceedings of the National Academy of Sciences, these wasps can guzzle seemingly unlimited amounts of ethanol regularly and at very high concentrations with no ill effects—not even intoxication. They pretty much drank honeybees used in the same experiments under the table.

“To the best of our knowledge, Oriental hornets are the only animal in nature adapted to consuming alcohol as a metabolic fuel,” said co-author Eran Levin of Tel Aviv University. “They show no signs of intoxication or illness, even after chronically consuming huge amounts of alcohol, and they eliminate it from their bodies very quickly.”

Per Levin et al., there’s a “drunken monkey” theory that predicts that certain animals well-adapted to low concentrations of ethanol in their diets nonetheless have adverse reactions at higher concentrations. Studies have shown that tree shrews, for example, can handle concentrations of up to 3.8 percent, but in laboratory conditions, when they consumed ethanol in concentrations of 10 percent or higher, they were prone to liver damage.

Similarly, fruit flies are fine with concentrations up to 4 percent but have increased mortality rates above that range. They’re certainly capable of drinking more: fruit flies can imbibe half their body volume in 15 percent (30 proof) alcohol each day. Not even spiking the ethanol with bitter quinine slows them down. Granted, they have ultra-fast metabolisms—the better to burn off the booze—but they can still become falling-down drunk. And fruit flies vary in their tolerance for alcohol depending on their genetic makeup—that is, how quickly their bodies adapt to the ethanol, requiring them to inhale more and more of it to achieve the same physical effects, much like humans.

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