Science

Scientists Map Miles of Wiring in a Speck of Mouse Brain

Published

1 month ago

April 9, 2025

Scientists Map Miles of Wiring in a Speck of Mouse Brain

The human brain is so complex that scientific brains have a hard time making sense of it. A piece of neural tissue the size of a grain of sand might be packed with hundreds of thousands of cells linked together by miles of wiring. In 1979, Francis Crick, the Nobel-prize-winning scientist, concluded that the anatomy and activity in just a cubic millimeter of brain matter would forever exceed our understanding.

“It is no use asking for the impossible,” Dr. Crick wrote.

Forty-six years later, a team of more than 100 scientists has achieved that impossible, by recording the cellular activity and mapping the structure in a cubic millimeter of a mouse’s brain — less than one percent of its full volume. In accomplishing this feat, they amassed 1.6 petabytes of data — the equivalent of 22 years of nonstop high-definition video.

“This is a milestone,” said Davi Bock, a neuroscientist at the University of Vermont who was not involved in the study, which was published Wednesday in the journal Nature. Dr. Bock said that the advances that made it possible to chart a cubic millimeter of brain boded well for a new goal: mapping the wiring of the entire brain of a mouse.

“It’s totally doable, and I think it’s worth doing,” he said.

More than 130 years have passed since the Spanish neuroscientist Santiago Ramón y Cajal first spied individual neurons under a microscope, making out their peculiar branched shapes. Later generations of scientists worked out many of the details of how a neuron sends a spike of voltage down a long arm, called an axon. Each axon makes contact with tiny branches, or dendrites, of neighboring neurons. Some neurons excite their neighbors into firing voltage spikes of their own. Some quiet other neurons.

Human thought somehow emerges from this mix of excitation and inhibition. But how that happens has remained a tremendous mystery, largely because scientists have been able to study only a few neurons at a time.

In recent decades, technological advances have allowed scientists to start mapping brains in their entirety. In 1986, British researchers published the circuitry of a tiny worm, made up of 302 neurons. In subsequent years, researchers charted bigger brains, such as the 140,000 neurons in the brain of a fly.

Could Dr. Crick’s impossible dream be possible after all? In 2016, the American government began a $100 million effort to scan a cubic millimeter of a mouse brain. The project — called Machine Intelligence from Cortical Networks, or MICrONS — was led by scientists at the Allen Institute for Brain Science, Princeton University and Baylor College of Medicine.

The researchers zeroed in on a portion of the mouse brain that receives signals from the eyes and reconstructs what the animal sees. In the first stage of the research, the team recorded the activity of neurons in that region as it showed a mouse videos of different landscapes.

The researchers then dissected the mouse brain and doused the cubic millimeter with hardening chemicals. Then they shaved off 28,000 slices from the block of tissue, capturing an image of each one. Computers were trained to recognize the outlines of cells in each slice and link the slices together into three-dimensional shapes. All told, the team charted 200,000 neurons and other types of brain cells, along with 523 million neural connections.

For Nuno da Costa, a biologist at the Allen Institute and one of the leaders of the project, just watching the cells take shape on his computer screen was breathtaking. “These neurons are absolutely stunning — it gives me pleasure,” he said.

To understand how this mesh of neurons functioned, Dr. da Costa and his colleagues mapped the activity that had been recorded when the mouse looked at videos.

“Imagine that you come to a party that has 80,000 people, and you can be aware of every conversation, but you don’t know who is talking to whom,” Dr. da Costa said. “And now imagine that you have a way to know who is talking to whom, but you have no idea what they’re saying. If you have these two things, you can tell a better story about what’s happening at the party.”

Analyzing the data, the researchers discovered patterns in the wiring of the brain that had escaped notice until now. They identified distinct kinds of inhibitory neurons, for instance, that link only to certain other types of neurons.

“When you go into studying the brain, it seems kind of hopeless — there are just so many connections and so much complexity,” said Mariela Petkova, a biophysicist at Harvard who was not involved in the MICrONS project. “Finding wiring rules is a win. The brain is a lot less messy than people thought,” she said.

Many of the MICrONS researchers are now pitching in on a bigger project: mapping an entire mouse’s brain. With a volume of 500 cubic millimeters, a full brain would take decades or centuries to chart with current methods. The scientists will have to find additional tricks in order to finish the project in a decade.

“What they’ve already had to do to get here is heroic,” said Gregory Jefferis, a neuroscientist at the University of Cambridge who was not involved in the MICrONS project. “But we’ve still got a mountain to climb.”

Forrest Collman, a member of the MICrONS project at the Allen Institute, is optimistic. He and his colleagues recently discovered how to make microscopically thin sections from an entire mouse brain. “Some of these barriers are starting to fall,” Dr. Collman said.

But our own brain, which is about a thousand times bigger than a mouse’s, presents a much bigger challenge, he added. “The human brain right now feels like outside the range of what is possible,” he said. “We are not going there anytime soon.”

But Sebastian Seung, a neuroscientist at Princeton and a member of the MICrONS project, noted that mouse brains and human brains are similar enough that researchers might glean clues that could help them find medications to effectively treat psychological disorders without causing harmful side effects.

“Our current methods of manipulating the nervous system are incredibly blunt instruments,” Dr. Seung said. “You put in a drug, and it goes everywhere,” he added. “But being able to actually reach in and manipulate a cell type — that’s precision.”

The efforts to map a whole mouse brain are supported by funding from a long-running National Institutes of Health program called the BRAIN initiative. But the future of the endeavor is uncertain. Last year, Congress cut funding to the BRAIN initiative by 40 percent, and last month President Trump signed a bill cutting support by another 20 percent.

Dr. Bock noted that brain-mapping efforts like MICrONS take years, partly because they require the invention of new technologies and software along the way.

“We need consistency and predictability of science funding to realize these long-term goals,” Dr. Bock said.

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Science

Behind a Museum Door, These Beetles Are Eating Flesh for Science

Published

4 hours ago

May 13, 2025

Press Room

Behind a Museum Door, These Beetles Are Eating Flesh for Science

Deep in the labyrinth of the American Museum of Natural History, past the giant suspended blue whale and the first floor’s Alaska brown bears, is an unobtrusive locked door. On it, there is a small sign.

“Bug Colony.”

Behind the door, accessible only to a handful of museum employees, thousands of flesh-eating dermestid beetles toil around the clock handling a task of specimen preparation that even the museum’s best trained specialists cannot.

They eat the meat off animal skeletons, leaving only clean bones behind.

Since many skeletons are too fine to be cleaned by human hands, the museum’s osteological preparation team turns to the six-legged staffers to prepare them for research and display.

The work is carried out in three gray wooden boxes the size of footlockers that house the colony. They are lined with stainless steel and their flip-up tops reveal beetles swarming the earthly remains of various small animals, mostly birds. They feast upon the gobbets of flesh clinging to the carcasses.

The room is pervaded by the soft, crackling sound of gnawing. “It sounds like something frying, or Rice Krispies when you add milk,” said Rob Pascocello, the colony’s tender.

The beetles are tiny enough — just a few millimeters long — to crawl into the recesses of the smallest animals and nibble away without affecting delicate skeletal structures, said Scott Schaefer, who oversees the museum’s collection of more than 30 million specimens and objects.

“They do the fine, detailed work that cannot be done by hand, because it’s so delicate,” Mr. Schaefer said. “It’s gentler than boiling a specimen or soaking it in chemicals or acid.”

Museum officials say the ravenous colony has processed most of the bird collections’ more than 30,000 skeleton specimens over the decades, plus countless other forms of carrion. “They get into the small crevices and, if left unchecked, keep eating until there’s nothing left to eat,” Mr. Schaefer said.

On a recent weekday, Paul Sweet, collection manager for the ornithology department, stood in the Bug Room, and in the interest of scientific precision pointed out that its name was imprecise.

True bugs, known to their fans as the Hemiptera order, have mouthparts that pierce and suck. Beetles — Coleoptera — are typically cylindrical and have mouthparts that chew.

The colony had gone to town with those mouthparts to reduce a once-lustrous pink flamingo to a humble bone bundle. A regal snowy owl was similarly picked clean. Then there was the small skeleton in a canister, with bones tinier than toothpicks.

“That’s a songbird,” said Mr. Pascocello.

Dermestid beetles are scavengers often found in the wild on animal carcasses, and in the nests, webs and burrows of animals.

Museum officials told The New York Times in 1979 that their dermestid colony had remained self-sustaining since being brought over from Africa in the 1930s. Mr. Sweet said the current group has been around for his entire 35 years at the museum, but could not say for sure if they were the original colony’s descendants.

Either way, since a beetle’s life is only about six months, “they’re all kissing cousins,” said Mr. Pascocello. He said that while the museum was closed during the coronavirus pandemic, he “kept a backup colony in my bedroom.”

On this day, Mr. Sweet was looking to skeletonize a northern gannet, a sea bird recovered from Midland Beach on Staten Island. It had been skinned, dried, and trimmed of most of its flesh by researchers before it was handed over to the colony for finishing work.

Within minutes, the carcass was swarmed. The beetles can pick clean a small bird within a couple of days, but may need two weeks for larger skeletons like the gannet.

Mr. Pascocello once served the beetles an orangutan; Mr. Sweet once gave them an emu. But the size of the beetles’ boxes is a factor. Larger specimens must be served piecemeal, like the carcass of a feisty Cuban crocodile known as Fidel, obtained from the Bronx Zoo in 2005.

Before the pristine skeletons are boxed and cataloged, they are soaked in water and frozen for days to kill remaining beetles or eggs.

The beetles are not a threat to humans, but an infestation of the museum’s specimen collection would be disastrous. Keeping the beetles well fed discourages them from wandering away, as does a strip of Vaseline toward the top of their boxes and a sticky floor section across the room’s doorway.

If the supply of specimens should stall, Mr. Pascocello keeps some chicken around as emergency food. Mr. Sweet said he offered the colony pigs’ feet during the pandemic because it was the cheapest bone meat at the supermarket.

The gourmandising of the beetles is a reminder that important science is not always conducted in gleaming, hygienic laboratories. On the door, under the “Bug Colony” sign, is a handwritten addendum:

“Bad odors emanating from behind this door is normal.”

Science

Researchers find drinking water is safe in Eaton, Palisades burn areas as utilities lift last 'do not drink' order

Published

7 hours ago

May 13, 2025

Press Room

Researchers find drinking water is safe in Eaton, Palisades burn areas as utilities lift last 'do not drink' order

Scientists have released some of the first independent test results confirming that drinking water in fire-affected areas around Altadena and the Pacific Palisades is largely free of harmful contaminants, as an Altadena utility lifted the last “do not drink” notice left in the burn zones.

Researchers with the LA Fire HEALTH Study released results on Friday from 53 homes spread across the burn areas and the more than three miles surrounding them. They found only one with a toxic substance at dangerous levels: at one home, the water contained benzene, a known carcinogen, at concentrations slightly above the state’s allowable level of 1 part per billion.

The findings add to mounting evidence that the affected area’s drinking water is safe. In March, Caltech professor Francois Tissot’s team found no lead levels above the U.S. Environmental Protection Agency’s limit in the tap water of the 43 homes they tested in Altadena and surrounding communities. Separately, UCLA professor Sanjay Mohanty’s group found no concerning levels of heavy metals or potentially harmful “forever” chemicals in 45 homes tested in the Palisades.

Experts noted that LA Fire HEALTH Study’s elevated benzene level — at 1.6 ppb — remains below the federal limit of 5 ppb and would likely drop below 1 ppb once the homeowner follows the utilities’ recommendation to run all faucets in the entire house for at least five minutes to flush contaminants out of the lines before using the tap water.

The state’s limit of 1 ppb equates to no more than a two-in-one-million chance of a resident developing cancer from a lifetime exposure to the contaminant at that level, according to the State Water Resources Control Board. For higher, short-term exposures to benzene, the U.S. EPA says exposure to over 200 ppb for more than a day could have negative, non-cancer health consequences for children.

“I’m optimistic from these results,” said Chris Olivares, a professor of civil and environmental engineering at the University of California, Irvine, who has led the tap water-testing part of the LA Fire HEALTH Study. “The major takeaway, I think, is the importance of flushing.”

Andrew Whelton — a professor of civil and environmental engineering at Purdue University and a pioneer in the field of post-fire water contamination and remediation — attributes the quick and successful restoration of safe drinking water to the hard work of local utilities and state regulators, which followed a post-fire playbook Whelton and others developed in the wake of the 2017 Tubbs fire in Santa Rosa, 2018 Camp fire in Paradise, and subsequent fires throughout Colorado in 2021 and Hawaii in 2023.

The way dangerous volatile organic compounds, like benzene, could contaminate water supplies after a wildfire wasn’t well known or studied until a Santa Rosa resident reported a strong smell of gasoline — a signature indicator of benzene — when turning on their kitchen faucet for the first time after the 2017 fire.

Scientists and public health officials raced to understand and solve the problem. They found benzene levels as high as 40,000 ppb, and it took a year to restore safe water.

After the Camp fire, scientists found levels over 900 ppb, which took eight months to remediate.

After the L.A. County fires, the Los Angeles Department of Water and Power found one instance of benzene at 71.3 ppb. The utility worked around the clock to restore safe water, first by closing roughly 4,800 open connections at fire hydrants and destroyed homes to restore water pressure, then continuously flushing water out of the system to push out contaminants. As they went, they tested and retested until benzene levels dropped to near-zero.

LADWP — with the approval of the State Water Resources Control Board — lifted its “do not drink” notice on March 7, exactly two months after the Palisades fire broke out. Two of the three smaller customer-owned utilities in Altadena, Lincoln Avenue Water Co. and Rubio Cañon Land and Water Assn. — which also detected benzene in their systems after the fires — quickly followed. The third, Las Flores Water Co., lifted the last “do not drink” notice on May 9.

Las Flores had registered the highest benzene levels of all the utilities: 440 ppb from a sample collected on April 10.

The LA Fire HEALTH Study team tested roughly eight homes within each burn area and over a dozen in adjacent communities between February and April while the testing and flushing process was ongoing.

The results are some of the first from the LA Fire HEALTH Study’s broad-ranging, privately funded effort between nearly a dozen academic and medical institutions, to understand the health consequences of the L.A. County fires over the course of 10 years.

Outside the burn areas, no homes the team sampled exceeded the state’s allowable limit for benzene or any of the other two dozen volatile organic compounds for which the group tested. And inside the burn areas, benzene was the only contaminant that exceeded the state’s allowable limits.

Although the utilities have worked for months to flush contaminants out of the labyrinth of pipes shuttling water from reservoirs to private properties, it’s homeowners who are responsible for finishing out the job and flushing the pipes on their own properties.

The researchers stressed that the one benzene exceedance — found in Lincoln Avenue’s service area one week after the utility’s “do not drink” notice was lifted — is a reminder that residents should follow the utilities’ guidance for safe water use once returning home.

“Lincoln Avenue Water Company’s top priority is to provide safe and reliable drinking water to the community. Through extensive testing, we have established that our system is in compliance with all state and federal water quality standards,” said Lincoln Avenue general manager Jennifer Betancourt Torres, in a statement to The Times.

“It’s important to emphasize that samples taken from inside the home are considered a representation of the residential plumbing and not the water being delivered,” she said.

The utilities and water safety experts say residents should first flush all of their lines — every faucet and spigot, both hot and cold, for at least five minutes. They should also run all appliances and fixtures, like dishwashers and washing machines, once with hot water before using. Two batches of ice from a fridge icemaker should be discarded.

Each utility is providing detailed, up-to-date guidance for their customers on their respective websites, including LADWP, Rubio Cañon, Lincoln Avenue and Las Flores.

Staff writer Ian James contributed to this report.

Science

An L.A. Doctor’s House Burned. Now He Treats the Fires’ Effects in Neighbors.

Published

22 hours ago

May 13, 2025

Press Room

An L.A. Doctor’s House Burned. Now He Treats the Fires’ Effects in Neighbors.

Another long-term concern is pulmonary fibrosis, a progressive disease in which scarring thickens and hardens lung tissue, making it difficult for oxygen to move into the bloodstream. Dr. Elsayegh describes a lung with pulmonary fibrosis as “a stiff balloon from the party store” — your face flushes as you try to force air inside, but it simply refuses to inflate.

As a former Palisades resident intent on returning to the neighborhood, Dr. Elsayegh is also doubling as a trusted confidant, drawing on his personal experience to help his patients face uncertainties and find solutions — or next steps, at least.

“In an ideal world, I would go in there and say, ‘Everyone that lives in the Palisades and in L.A. County, let’s all move. Let’s all go somewhere else and we don’t have to worry about this,’ ” he said. “That’s not reality. I’m trying to find this unbelievably difficult balance of helping us return to normalcy or return to our life, but doing it as safely as possible.”

In early February, Dr. Elsayegh pulled up a chair next to Dana Michels, a cybersecurity lawyer and healthy mother of three who had gone to check the damage at her house and now could not shake a cough.

“Sweetheart, you’re not moving air at all,” Dr. Elsayegh said, listening to her lungs through a stethoscope and quickly ordering a breathing test and a nebulizer, to start. A pulmonary student asked to take a listen, then glanced up at Dr. Elsayegh, looking confused.

“I’m not hearing anything,” the student said. Dr. Elsayegh gave a single nod.

After years of renting, Ms. Michels and her husband got their first mortgage almost four years ago; it was a family milestone. Now, with their Palisades home smoked through, the family is split between two rental apartments in Marina del Rey — one for boys, one for girls — and they are navigating a new school, new insurance paperwork and new prescriptions to manage the wheezing.