Posts Tagged ‘Neuron’

By Ashley Yeager

Researchers have transferred a memory from one snail to another via RNA, they report today (May 14) in eNeuro. If confirmed in other species, the finding may lead to a shift in scientists’ thinking about how memories are made—rather than cemented in nerve-cell connections, they may be spurred on by RNA-induced epigenetic changes.

“The study suggests that RNA populations are the missing link in the search for memory,” Bridget Queenan, a neuroscientist at the University of California, Santa Barbara, who was not involved in the study, writes in an email to The Scientist. “If circulating neural RNAs can transfer behavioral states and tendencies, orchestrating both the transient feeling and the more permanent memory, it suggests that human memory—just like mood—will only be explained by exploring the interplay between bodies and brains.”

For decades, researchers have tried to pinpoint how, when, and where memories form. In the 1940s, Canadian psychologist Donald Hebb proposed memories are made in the connections between neurons, called synapses, and stored as those connections grow stronger and more abundant. Experiments in the 1960s, however, suggested RNA could play a role in making memories, though the work was largely written off as irreproducible.

Study coauthor David Glanzman of the University of California, Los Angeles, has been working on the cell biology of learning and memory for nearly 40 years, and says for the majority of that time he believed memory was stored at synapses. Several years ago, though, he and his colleagues began replicating memory-erasing research done in rodents in California sea hares (Aplysia californica), a type of marine snail also called a sea slug. The team found that the snail synapses built to “store” a memory weren’t necessarily the synapses that were removed from the neural circuits in the memory-erasing experiments.

“It was completely arbitrary which synaptic connections got erased,” Glanzman says. “That suggested maybe the memory wasn’t stored at the synapse but somewhere else.”

Glanzman turned his attention to RNA because of those earlier hints it was related to memory, and also because of recent experiments suggesting long-term memory was stored in the cell bodies of neurons, not synapses. He picked Aplysia because it has been a longtime model organism for memory studies. Like all mollusks, these snails have groups of neurons called ganglia, rather than brains. Their nervous systems comprise about 20,000 neurons, and the cells are some of the biggest and easily identifiable among nerve cells in all animals. In the snail’s gut, for example, are specific sensory and motor neurons that control the withdrawal of a fleshy, spout-like organ on the snail’s back called a siphon and the contraction of a caterpillar-looking gill, which the animal uses to breathe.

When touched lightly on the siphon, the neurons fire, retract the tissue, and contract the gill within the body cavity for a few seconds to protect it against attack. Sticking electrodes in the snail’s tail and shocking it makes this defensive response last longer, tens of seconds, and sometimes up to almost a minute. By repeatedly shocking the snail’s tail, the animal learns to stay in that defensive position when touched on the siphon, even weeks after the shocks end.

In his team’s latest experiments, Glanzman and his colleagues zapped snails’ tails, then pulled the abdominal neurons from the shocked snails, extracted their RNA, dissolved the RNA into deionized water, and injected the solution into the necks of snails that had never been shocked. (For a control, the team also took RNA from non-shocked snails and injected into naive snails.) When tapped on the siphon 24 hours later, snails that got RNA from shocked snails withdrew their siphon and gill for significantly longer (almost 40 seconds) than did snails that got RNA from non-shocked animals (less than 10 seconds).

DNA methylation appeared to be essential for the transfer of the memory among snails. When Glanzman and his colleagues blocked DNA methylation in snails getting RNA from shocked ones, the injected snails withdrew their siphons for only a few seconds when tapped on the siphon.

Glanzman wanted to know if the RNA from shocked snails actually affected the neuronal connections of the snails receiving the injections any differently than RNA from nonshocked snails. So, in a third test, he and his team removed sensory neurons from nonshocked snails, cultured the cells in a dish, and then exposed the cells to RNA from shocked snails. Zapping the culture with a bit of current excited the sensory neurons much more than neurons treated with RNA from nonshocked snails. RNA from shocked snails also enhanced a subset of synapses between sensory and motor neurons in vitro, suggesting it was indeed the RNA that transported the memory, Glanzman explains.

The idea “seems quite radical as we don’t have a specific mechanism for how it works in a non-synaptic manner,” Bong-Kiun Kaang, a neuroscientist at Seoul National University who was not involved in the study, writes in an email to The Scientist. Kaang notes there are “many critical questions that need to be addressed to further validate the author’s argument,” such as what kinds of noncoding RNAs are specifically involved, how are the RNAs transferred among neurons, and how much do RNAs at the synapse play a role? The experiments should also be replicated in organisms other than snails, he says.

Glanzman says that in his next experiments he will attempt to identify the RNAs involved, and he has an idea for the mechanism, too. The memory is not stored in the RNA itself, he speculates—instead, noncoding RNA produces epigenetic changes in the nucleus of neurons, thereby storing the memory.

“This idea is probably going to strike most of my colleagues as extremely improbable,” Glanzman says. “But if we’re right, we’re just at the beginning of understanding how memory works.”

A. Bédécarrats et al., “RNA from trained Aplysia can induce an epigenetic engram for long-term sensitization in untrained Aplysia,” eNeuro,, 2018.


Futuristic cityscape maze.

By Diana Kwon

A computer program can learn to navigate through space and spontaneously mimics the electrical activity of grid cells, neurons that help animals navigate their environments, according to a study published May 9 in Nature.

“This paper came out of the blue, like a shot, and it’s very exciting,” Edvard Moser, a neuroscientist at the Kavli Institute for Systems Neuroscience in Norway who was not involved in the work, tells Nature in an accompanying news story. “It is striking that the computer model, coming from a totally different perspective, ended up with the grid pattern we know from biology.” Moser shared a Nobel Prize for the discovery of grid cells with neuroscientists May-Britt Moser and John O’Keefe in 2014.

When scientists trained an artificial neural network to navigate in the form of virtual rats through a simulated environment, they found that the algorithm produced patterns of activity similar to that found in the grid cells of the human brain. “We wanted to see whether we could set up an artificial network with an appropriate task so that it would actually develop grid cells,” study coauthor Caswell Barry of University College London, tells Quanta. “What was surprising was how well it worked.”

The team then tested the program in a more-complex, maze-like environment, and found that not only did the virtual rats make their way to the end, they were also able to outperform a human expert at the task.

“It is doing the kinds of things that animals do and that is to take direct routes wherever possible and shortcuts when they are available,” coauthor Dharshan Kumaran, a senior researcher at Google’s AI company DeepMind, tells The Guardian.

DeepMind researchers hope to use these types of artificial neural networks to study other parts of the brain, such as those involved in understanding sound and controlling limbs, according to Wired. “This has proven to be extremely hard with traditional neuroscience so, in the future, if we could improve these artificial models, we could potentially use them to understand other brain functionalities,” study coauthor Andrea Banino, a research scientist at DeepMind, tells Wired. “This would be a giant step toward the future of brain understanding.”

by Antonio Regalado

The startup accelerator Y Combinator is known for supporting audacious companies in its popular three-month boot camp.

There’s never been anything quite like Nectome, though.

Next week, at YC’s “demo days,” Nectome’s cofounder, Robert McIntyre, is going to describe his technology for exquisitely preserving brains in microscopic detail using a high-tech embalming process. Then the MIT graduate will make his business pitch. As it says on his website: “What if we told you we could back up your mind?”

So yeah. Nectome is a preserve-your-brain-and-upload-it company. Its chemical solution can keep a body intact for hundreds of years, maybe thousands, as a statue of frozen glass. The idea is that someday in the future scientists will scan your bricked brain and turn it into a computer simulation. That way, someone a lot like you, though not exactly you, will smell the flowers again in a data server somewhere.

This story has a grisly twist, though. For Nectome’s procedure to work, it’s essential that the brain be fresh. The company says its plan is to connect people with terminal illnesses to a heart-lung machine in order to pump its mix of scientific embalming chemicals into the big carotid arteries in their necks while they are still alive (though under general anesthesia).

The company has consulted with lawyers familiar with California’s two-year-old End of Life Option Act, which permits doctor-assisted suicide for terminal patients, and believes its service will be legal. The product is “100 percent fatal,” says McIntyre. “That is why we are uniquely situated among the Y Combinator companies.”

There’s a waiting list

Brain uploading will be familiar to readers of Ray Kurzweil’s books or other futurist literature. You may already be convinced that immortality as a computer program is definitely going to be a thing. Or you may think transhumanism, the umbrella term for such ideas, is just high-tech religion preying on people’s fear of death.

Either way, you should pay attention to Nectome. The company has won a large federal grant and is collaborating with Edward Boyden, a top neuroscientist at MIT, and its technique just claimed an $80,000 science prize for preserving a pig’s brain so well that every synapse inside it could be seen with an electron microscope.

McIntyre, a computer scientist, and his cofounder Michael McCanna have been following the tech entrepreneur’s handbook with ghoulish alacrity. “The user experience will be identical to physician-assisted suicide,” he says. “Product-market fit is people believing that it works.”

Nectome’s storage service is not yet for sale and may not be for several years. Also still lacking is evidence that memories can be found in dead tissue. But the company has found a way to test the market. Following the example of electric-vehicle maker Tesla, it is sizing up demand by inviting prospective customers to join a waiting list for a deposit of $10,000, fully refundable if you change your mind.

So far, 25 people have done so. One of them is Sam Altman, a 32-year-old investor who is one of the creators of the Y Combinator program. Altman tells MIT Technology Review he’s pretty sure minds will be digitized in his lifetime. “I assume my brain will be uploaded to the cloud,” he says.

Old idea, new approach

The brain storage business is not new. In Arizona, the Alcor Life Extension Foundation holds more than 150 bodies and heads in liquid nitrogen, including those of baseball great Ted Williams. But there’s dispute over whether such cryonic techniques damage the brain, perhaps beyond repair.

So starting several years ago, McIntyre, then working with cryobiologist Greg Fahy at a company named 21st Century Medicine, developed a different method, which combines embalming with cryonics. It proved effective at preserving an entire brain to the nanometer level, including the connectome—the web of synapses that connect neurons.

A connectome map could be the basis for re-creating a particular person’s consciousness, believes Ken Hayworth, a neuroscientist who is president of the Brain Preservation Foundation—the organization that, on March 13, recognized McIntyre and Fahy’s work with the prize for preserving the pig brain.

There’s no expectation here that the preserved tissue can be actually brought back to life, as is the hope with Alcor-style cryonics. Instead, the idea is to retrieve information that’s present in the brain’s anatomical layout and molecular details.

“If the brain is dead, it’s like your computer is off, but that doesn’t mean the information isn’t there,” says Hayworth.

A brain connectome is inconceivably complex; a single nerve can connect to 8,000 others, and the brain contains millions of cells. Today, imaging the connections in even a square millimeter of mouse brain is an overwhelming task. “But it may be possible in 100 years,” says Hayworth. “Speaking personally, if I were a facing a terminal illness I would likely choose euthanasia by [this method].”

A human brain

The Nectome team demonstrated the seriousness of its intentions starting this January, when McIntyre, McCanna, and a pathologist they’d hired spent several weeks camped out at an Airbnb in Portland, Oregon, waiting to purchase a freshly deceased body.

In February, they obtained the corpse of an elderly woman and were able to begin preserving her brain just 2.5 hours after her death. It was the first demonstration of their technique, called aldehyde-stabilized cryopreservation, on a human brain.

Fineas Lupeiu, founder of Aeternitas, a company that arranges for people to donate their bodies to science, confirmed that he provided Nectome with the body. He did not disclose the woman’s age or cause of death, or say how much he charged.

The preservation procedure, which takes about six hours, was carried out at a mortuary. “You can think of what we do as a fancy form of embalming that preserves not just the outer details but the inner details,” says McIntyre. He says the woman’s brain is “one of the best-preserved ever,” although her being dead for even a couple of hours damaged it. Her brain is not being stored indefinitely but is being sliced into paper-thin sheets and imaged with an electron microscope.

McIntyre says the undertaking was a trial run for what the company’s preservation service could look like. He says they are seeking to try it in the near future on a person planning doctor-assisted suicide because of a terminal illness.

Hayworth told me he’s quite anxious that Nectome refrain from offering its service commercially before the planned protocol is published in a medical journal. That’s so “the medical and ethics community can have a complete round of discussion.”

“If you are like me, and think that mind uploading is going to happen, it’s not that controversial,” he says. “But it could look like you are enticing someone to commit suicide to preserve their brain.” He thinks McIntyre is walking “a very fine line” by asking people to pay to join a waiting list. Indeed, he “may have already crossed it.”

Crazy or not ?

Some scientists say brain storage and reanimation is an essentially fraudulent proposition. Writing in our pages in 2015, the McGill University neuroscientist Michael Hendricks decried the “abjectly false hope” peddled by transhumanists promising resurrection in ways that technology can probably never deliver.

“Burdening future generations with our brain banks is just comically arrogant. Aren’t we leaving them with enough problems?” Hendricks told me this week after reviewing Nectome’s website. “I hope future people are appalled that in the 21st century, the richest and most comfortable people in history spent their money and resources trying to live forever on the backs of their descendants. I mean, it’s a joke, right? They are cartoon bad guys.”

Nectome has received substantial support for its technology, however. It has raised $1 million in funding so far, including the $120,000 that Y Combinator provides to all the companies it accepts. It has also won a $960,000 federal grant from the U.S. National Institute of Mental Health for “whole-brain nanoscale preservation and imaging,” the text of which foresees a “commercial opportunity in offering brain preservation” for purposes including drug research.

About a third of the grant funds are being spent in the MIT laboratory of Edward Boyden, a well-known neuroscientist. Boyden says he’s seeking to combine McIntyre’s preservation procedure with a technique MIT invented, expansion microscopy, which causes brain tissue to swell to 10 or 20 times its normal size, and which facilitates some types of measurements.

I asked Boyden what he thinks of brain preservation as a service. “I think that as long as they are up-front about what we do know and what we don’t know, the preservation of information in the brain might be a very useful thing,” he replied in an e-mail.

The unknowns, of course, are substantial. Not only does no one know what consciousness is (so it will be hard to tell if an eventual simulation has any), but it’s also unclear what brain structures and molecular details need to be retained to preserve a memory or a personality. Is it just the synapses, or is it every fleeting molecule? “Ultimately, to answer this question, data is needed,” Boyden says.

Demo day

Nectome has been honing its pitch for Y Combinator’s demo days, trying to create a sharp two-minute summary of its ideas to present to a group of elite investors. The team was leaning against showing an image of the elderly woman’s brain. Some people thought it was unpleasant. The company had also walked back its corporate slogan, changing it from “We archive your mind” to “Committed to the goal of archiving your mind,” which seemed less like an overpromise.

McIntyre sees his company in the tradition of “hard science” startups working on tough problems like quantum computing. “Those companies also can’t sell anything now, but there is a lot of interest in technologies that could be revolutionary if they are made to work,” he says. “I do think that brain preservation has amazing commercial potential.”

He also keeps in mind the dictum that entrepreneurs should develop products they want to use themselves. He sees good reasons to save a copy of himself somewhere, and copies of other people, too.

“There is a lot of philosophical debate, but to me a simulation is close enough that it’s worth something,” McIntyre told me. “And there is a much larger humanitarian aspect to the whole thing. Right now, when a generation of people die, we lose all their collective wisdom. You can transmit knowledge to the next generation, but it’s harder to transmit wisdom, which is learned. Your children have to learn from the same mistakes.”

“That was fine for a while, but we get more powerful every generation. The sheer immense potential of what we can do increases, but the wisdom does not.”

A key metabolic pathway must be switched off during neuron development or fewer neurons (green, on the right) survive.

by Jennifer Hicks

Researchers at the Salk Institute of Biological Studies released a study in the July 12 issue of eLife, which identifies the point at which there’s a dramatic metabolic shift in developing neurons. This discovery of the path a neuron takes during development could help provide insight into neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

In a press release, Tony Hunter, American Cancer Society Professor, Salk Molecular and Cell Biology Laboratory said there’s relatively little understanding about how neuron metabolism is first established.

Oxidative stress leads to disruptions in neural cells which are key players in neurodegenerative diseases like Parkinson’s or ALS. The brain needs oxygen to survive but by knowing when and how neuron metabolism goes off track and mitochondria fail to function properly in these diseases, researchers can begin to devise ways to re-route metabolic processes to prevent degeneration.

“Aside from enabling us to understand this process during neuronal development, the work also allows us to better understand neurodegenerative disease,” added Hunter.

What the researchers found in the study was that while neurons shut off the aerobic glycolysis to survive during the metabolic process at the same time neurons also had to kick-start oxidative phosphorylation in order to survive. When the researchers stopped that metabolic process from happening, the neurons died. A neuron dysfunction of any kind can potentially lead to neurodegenerative disease for a number of reasons.

By Clare Wilson

It is one of life’s great enigmas: why do we sleep? Now we have the best evidence yet of what sleep is for – allowing housekeeping processes to take place that stop our brains becoming overloaded with new memories.

All animals studied so far have been found to sleep, but the reason for their slumber has eluded us. When lab rats are deprived of sleep, they die within a month, and when people go for a few days without sleeping, they start to hallucinate and may have epileptic seizures.

One idea is that sleep helps us consolidate new memories, as people do better in tests if they get a chance to sleep after learning. We know that, while awake, fresh memories are recorded by reinforcing connections between brain cells, but the memory processes that take place while we sleep have remained unclear.

Support is growing for a theory that sleep evolved so that connections in the brain can be pruned down during slumber, making room for fresh memories to form the next day. “Sleep is the price we pay for learning,” says Giulio Tononi of the University of Wisconsin-Madison, who developed the idea.

Now we have the most direct evidence yet that he’s right. Tononi’s team measured the size of these connections or synapses in brain slices taken from mice. The synapses in samples taken at the end of a period of sleep were 18 per cent smaller than those in samples taken from before sleep, showing that the synapses between neurons are weakened during slumber.

A good night’s sleep

Tononi announced these findings at the Federation of European Neuroscience Societies meeting in Copenhagen, Denmark, last week. “The data was very solid and well documented,” says Maiken Nedergaard of the University of Rochester, who attended the conference.

“It’s an extremely elegant idea,” says Vladyslav Vyazovskiy of the University of Oxford

If the housekeeping theory is right, it would explain why, when we miss a night’s sleep, the next day we find it harder to concentrate and learn new information – we may have less capacity to encode new experiences. The finding suggests that, as well as it being important to get a good night’s sleep after learning something, we should also try to sleep well the night before.

It could also explain why, if our sleep is interrupted, we feel less refreshed the next day. There is some indirect evidence that deep, slow-wave sleep is best for pruning back synapses, and it takes time for our brains to reach this level of unconsciousness.

Waking refreshed

Previous evidence has also supported the housekeeping theory. For instance, EEG recordings show that the human brain is less electrically responsive at the start of the day – after a good night’s sleep – than at the end, suggesting that the connections may be weaker. And in rats, the levels of a molecule called the AMPA receptor – which is involved in the functioning of synapses – are lower at the start of their wake periods.

The latest brain-slice findings that synapses get smaller is the most direct evidence yet that the housekeeping theory is right, says Vyazovskiy. “Structural evidence is very important,” he says. “That’s much less affected by other confounding factors.”

Protecting what matters

Getting this data was a Herculean task, says Tononi. They collected tiny chunks of brain tissue, sliced it into ultrathin sections and used these to create 3D models of the brain tissue to identify the synapses. As there were nearly 7000 synapses, it took seven researchers four years.

The team did not know which mouse was which until last month, says Tononi, when they broke the identification code, and found their theory stood up.

“People had been working for years to count these things. You start having stress about whether it’s really possible for all these synapses to start getting fatter and then thin again,” says Tononi.

The team also discovered that some synapses seem to be protected – the biggest fifth stayed the same size. It’s as if the brain is preserving its most important memories, says Tononi. “You keep what matters.”

Infection with the common parasite Toxoplasma gondii promotes accumulation of a neurotransmitter in the brain called glutamate, triggering neurodegenerative diseases in individuals predisposed to such conditions.

Written by Honor Whiteman

This is the finding of a new study conducted by researchers from the University of California-Riverside (UC-Riverside), recently published in PLOS Pathogens.

T. gondii is a single-celled parasite that can cause a disease known as toxoplasmosis.

Infection with the parasite most commonly occurs through eating undercooked, contaminated meat or drinking contaminated water.

It may also occur through accidentally swallowing the parasite after coming into contact with cat feces – by cleaning a litter tray, for example.

Though more than 60 million people in the United States are believed to be infected with T. gondii, few people become ill from it; a healthy immune system can normally stave it off.

As such, most people who become infected with the parasite are unaware of it.

Those who do become ill from T. gondii infection may experience flu-like symptoms – such as swollen lymph glands or muscle aches – that last for at least a month.

In severe cases, toxoplasmosis can cause damage to the eyes, brain, and other organs, though such complications usually only arise in people with weakened immune systems.

The new study, however, suggests there may be another dark side to T. gondii infection: it may lead to development of neurodegenerative disease in people who are predisposed to it.

To reach their findings, lead author Emma Wilson – an associate professor in the Division of Biomedical Sciences at the UC-Riverside School of Medicine – and colleagues focused on how T. gondii infection in mice affects glutamate production

How a build-up of glutamate can damage the brain

Glutamate is an amino acid released by nerve cells, or neurons. It is one of the brain’s most abundant excitatory neurotransmitters, aiding communication between neurons.

However, previous studies have shown that too much glutamate may cause harm; a build-up of glutamate is often found in individuals with traumatic brain injury (TBI) and people with certain neurodegenerative diseases, such as multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS).

The researchers explain that excess glutamate accumulates outside of neurons, and this build-up is regulated by astrocytes – cells in the central nervous system (CNS).

Astrocytes use a glutamate transporter called GLT-1 in an attempt to remove excess glutamate from outside of neurons and convert it into a less harmful substance called glutamine, which cells use for energy.

“When a neuron fires, it releases glutamate into the space between itself and a nearby neuron,” explains Wilson. “The nearby neuron detects this glutamate, which triggers a firing of the neuron. If the glutamate isn’t cleared by GLT-1 then the neurons can’t fire properly the next time and they start to die.”

T. gondii increases glutamate by inhibiting GLT-1

n mice infected with T. gondii, the researchers identified an increase in glutamate levels.

They found that the parasite causes astrocytes to swell, which impairs their ability to regulate glutamate accumulation outside of neurons.

Furthermore, the parasite prevents GLT-1 from being properly expressed, which causes an accumulation of glutamate and misfiring of neurons. This may lead to neuronal death, and ultimately, neurodegenerative disease.

“These results suggest that in contrast to assuming chronic Toxoplasma infection as quiescent and benign, we should be aware of the potential risk to normal neurological pathways and changes in brain chemistry.” – Emma Wilson

Next, the researchers gave the infected mice an antibiotic called ceftriaxone, which has shown benefits in mouse models of ALS and a variety of CNS injuries.

They found the antibiotic increased expression of GLT-1, which led to a reduction in glutamate build-up and restored neuronal function.

Wilson says their study represents the first time that T. gondii has been shown to directly disrupt a key neurotransmitter in the brain.

“More direct and mechanistic research needs to be performed to understand the realities of this very common pathogen,” she adds.

While their findings indicate a link between T. gondii infection and neurodegenerative disease, Wilson says they should not be cause for panic.

“We have been living with this parasite for a long time,” she says. “It does not want to kill its host and lose its home. The best way to prevent infection is to cook your meat and wash your hands and vegetables. And if you are pregnant, don’t change the cat litter.”

The team now plans to further investigate what causes the reduced expression of GLT-1 in T. gondii infection.

There’s an old saying in neuroscience: neurons that fire together wire together. This means the more you run a neuro-circuit in your brain, the stronger that circuit becomes. This is why, to quote another old saw, practice makes perfect. The more you practice piano, or speaking a language, or juggling, the stronger those circuits get.

For years this has been the focus for learning new things. But as it turns out, the ability to learn is about more than building and strengthening neural connections. Even more important is our ability to break down the old ones. It’s called “synaptic pruning.” Here’s how it works.

Imagine your brain is a garden, except instead of growing flowers, fruits, and vegetables, you grow synaptic connections between neurons. These are the connections that neurotransmitters like dopamine, seratonin, and others travel across.

“Glial cells” are the gardeners of your brain—they act to speed up signals between certain neurons. But other glial cells are the waste removers, pulling up weeds, killing pests, raking up dead leaves. Your brain’s pruning gardeners are called “microglial cells.” They prune your synaptic connections. The question is, how do they know which ones to prune?

Researchers are just starting to unravel this mystery, but what they do know is the synaptic connections that get used less get marked by a protein, C1q (as well as others). When the microglial cells detect that mark, they bond to the protein and destroy—or prune—the synapse.

This is how your brain makes the physical space for you to build new and stronger connections so you can learn more.

Have you ever felt like your brain is full? Maybe when starting a new job, or deep in a project. You’re not sleeping enough, even though you’re constantly taking in new information. Well, in a way, your brain actually is full

When you learn lots of new things, your brain builds connections, but they’re inefficient, ad hoc connections. Your brain needs to prune a lot of those connections away and build more streamlined, efficient pathways. It does that when we sleep.

Your brain cleans itself out when you sleep—your brain cells shrinking by up to 60% to create space for your glial gardeners to come in take away the waste and prune the synapses.

Have you ever woken up from a good night’s rest and been able to think clearly and quickly? That’s because all the pruning and pathway-efficiency that took place overnight has left you with lots of room to take in and synthesize new information—in other words, to learn.

This is the same reason naps are so beneficial to your cognitive abilities. A 10- or 20-minute nap gives your microglial gardeners the chance to come in, clear away some unused connections, and leave space to grow new ones.

Thinking with a sleep-deprived brain is like hacking your way through a dense jungle with a machete. It’s overgrown, slow-going, exhausting. The paths overlap, and light can’t get through. Thinking on a well-rested brain is like wandering happily through Central Park; the paths are clear and connect to one another at distinct spots, the trees are in place, you can see far ahead of you. It’s invigorating.

And in fact, you actually have some control over what your brain decides to delete while you sleep. It’s the synaptic connections you don’t use that get marked for recycling. The ones you do use are the ones that get watered and oxygenated. So be mindful of what you’re thinking about.

If you spend too much time reading theories about the end of Game of Thrones and very little on your job, guess which synapses are going to get marked for recycling?

If you’re in a fight with someone at work and devote your time to thinking about how to get even with them, and not about that big project, you’re going to wind up a synaptic superstar at revenge plots but a poor innovator.

To take advantage of your brain’s natural gardening system, simply think about the things that are important to you. Your gardeners will strengthen those connections and prune the ones that you care about less. It’s how you help the garden of your brain flower.