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Scientists Map Miles of Wiring in a Speck of Mouse Brain

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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.

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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.

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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.

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“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.”

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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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This plant extract can make a lethal drug cocktail. Can it also treat opioid addiction?

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This plant extract can make a lethal drug cocktail. Can it also treat opioid addiction?

A plant extract that’s gaining popularity as a pain cure-all and has been associated with multiple California deaths in its concentrated, synthetic form has been approved for research as a treatment for opioid addiction by the federal government.

Kratom is derived from the leaves of Mitragyna speciosa, a tree native to Southeast Asia, and is commonly made into a powder or pill.

Researchers say people in the U.S. are using kratom to alleviate anxiety, treat chronic pain or as a remedy for the symptoms associated with quitting opioids, due to its ability to bind with opioid receptors in the body. But recently, public health officials have raised alarms about a component of the leaf called 7-hydroxymitragynine, also known as 7-OH, an alkaloid that has the potential for abuse and addiction in high doses.

Last year, the Los Angeles County Public Health Department linked the deaths of six county residents to the use of 7-OH mixed with other substances. The toxicology screens for some of the deceased revealed both kratom and 7-OH, leading to a countywide crackdown of products with either compound because they’re unregulated.

Although there is no scientific consensus on whether kratom has therapeutic value, the Food and Drug Administration has recommended that its potent 7-OH form be classified as a controlled substance. Consumers who use 7-OH as a pain reliever expecting an experience similar to consuming kratom are at risk, said Dr. Mason Turner, president-elect of the California Society of Addiction Medicine.

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“I have a couple of patients that I work with who use 7-OH for chronic pain management, not realizing the potential of the medication, and then developed an opioid use disorder,” Turner said. “I think in that case it was very clear they were seeking it for the chronic pain, not to get high, not to have some kind of experience, but really to reduce their pain.”

About two decades ago, Turner said, the healthcare industry started acknowledging the limits and risks of prescribing opioids for chronic pain. Some doctors pulled back on prescriptions, recognizing the potential for abuse.

That led some patients to find alternative solutions, he said.

“Maybe they don’t get a good benefit, or maybe the benefit from some of the other treatments is not as robust as what they got from opioids,” Turner said. “So they seek out some of these illicit products … or they look for kratom or 7-OH to be able to mitigate the pain.”

Turner said he supports further research into kratom and regulation because “it could be worth exploring as a treatment for chronic pain.”

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On June 1, the National Institutes of Health announced that researchers from the University of Florida would begin the first phase of clinical trials on kratom to evaluate it as a potential treatment for opioid addiction. The research would be done with the FDA’s approval, according to officials.

“This … is a major step toward expanding treatment options for the millions of Americans struggling with opioid use disorder, which has contributed to historically high overdose mortality rates,” said Dr. Nora Volkow, director of NIH’s National Institute on Drug Abuse, in a statement.

Interest in kratom surged in the last couple of years as users have reported consuming the compound in the form of a pill, powder or tea to treat various ailments. A John Hopkins survey conducted in 2020 reported that 91% of respondents used kratom to treat chronic pain, 67% to treat anxiety, 64% for depression and 41% to treat opioid dependence.

A more recent study by the University of Michigan and Texas State University found that more than 5 million people in the U.S., including more than 100,000 children ages 12 to 17, have used kratom, the compound experts say is growing in popularity with young adults.

In the study, which analyzed data from the National Survey on Drug Use and Health collected between 2021 and 2024, researchers say that despite numerous state-level bans on kratom across the nation, its use is at an all-time high and is increasing.

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People between the ages of 21 and 34 said they used kratom at least once and 1% said they used it in the last year. The share of children ages 12 and older who said they had used kratom increased from 1.6% in 2021 to 1.9% in 2024.

The FDA has stated that neither kratom nor 7-OH are approved as drug products, dietary supplements or food additives, but that hasn’t stopped storefronts and companies from selling them as such.

Up until November you could find kratom and 7-OH products in smoke shops and specialty stores in California, but that has stopped.

“Until kratom and its pharmacologically active key ingredients mitragynine and 7-OH are approved for use, they will remain classified as adulterants in drugs, dietary supplements and foods,” the California Department of Public Health told The Times via email.

Kratom “Feel Free Classic” liquid products are displayed at a smoke shop in Los Angeles in 2024 before they were banned.

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(Michael Blackshire / Los Angeles Times)

In May, the California Department of Public Health and Atty. Gen. Rob Bonta filed a complaint against Ashlynn Marketing Group Inc., accusing the company of repeatedly flouting the state’s regulations on kratom products.

The filing, submitted in the San Diego County Superior Court, seeks a judge’s order to condemn and destroy the embargoed kratom products, halt ongoing unlawful manufacturing and impose civil penalties.

The California Department of Public Health “is pursuing legal action because Ashlynn’s continued manufacture and sale of these products pose a clear and preventable public‑health risk and violates state and federal law,” said Dr. Erica Pan, the department’s director and state public health officer. “7-OH and kratom-derived products have been associated with addiction, serious health harms, overdose and death.”

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The state is alleging its inspectors visited Ashlynn Marketing Group’s facility in Santee in May 2025 and found kratom powders, capsules, liquids and chewable tablets being manufactured and held for sale.

During the visit, inspectors issued an embargo to prohibit the sale and distribution of all kratom-related materials on-site, according to the complaint.

Public health inspectors conducted follow-up visits at the facility in October and April, “collecting evidence at both inspections that indicated embargoed kratom products had been moved, tampered with and repackaged,” according to public health officials.

“In addition, investigators observed evidence of continued manufacturing and distribution of kratom materials,” officials said. “The firm’s owner continues to manufacture kratom products and ships orders weekly.”

To date, the California Department of Public Health has seized more than $5 million worth of kratom and 7-OH products, a spokesperson for the department told The Times.

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California and Los Angeles County are considering whether to tighten regulations or ban the compounds altogether.

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Scientists find a whale graveyard in the Indian Ocean that’s millions of years old

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Scientists find a whale graveyard in the Indian Ocean that’s millions of years old

Scientists have unearthed communities of marine life — including jellyfish, tubeworms and brittle stars — thriving on a whale graveyard that is millions of years old.

These graveyards form when whale carcasses fall to the sea floor, becoming a sustaining snack for nearby critters. This one, located up to 23,000 feet below the surface of the southeastern Indian Ocean, spans the largest area and is so far the deepest and oldest found.

A whale’s sheer size and the unique chemistry of its bones are the keys to forming these unique underwater neighborhoods, said Xikun Song, a biologist with the Chinese Academy of Sciences’ Institute of Deep-sea Science and Engineering.

“At the same time, the very nature of the deep ocean makes these sites exceptionally difficult for scientists to locate,” Song, who was involved with the latest find, wrote in an email.

Researchers explored the remains during multiple deep-sea submersible trips in 2023, collecting samples and mapping the extent of the necropolis. They found five carcass sites and fossils, including skulls belonging to beaked and baleen whales. The oldest bones date back 5.3 million years.

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Feeding and living on the carcasses were myriad creatures, large and small, including sea cucumbers, squat lobsters and saltwater clams. Many of them are likely species that have never been documented, according to findings published Wednesday in the journal Nature.

“The potential number of specimens is just astounding,” said paleontologist Stephen Godfrey with the Calvert Marine Museum in Maryland, who wasn’t involved in the research.

Many factors likely conspired to preserve the bones for millions of years, according to the study authors. They’re dense enough to outlast attacks from bone-eating worms, and located deep enough in the ocean to avoid getting buried by dust and loose particles. The bones also were coated with a light layer of minerals from the surrounding seawater, which may have prevented them from degrading.

Why did so many whales die here? Maybe they were already living in the area and died of natural causes. A few could have perished from exhaustion or illness caused by deep-sea diving. The area’s shape, akin to the letter V, could also have funneled the remains to their resting spot, the authors wrote.

Such discoveries are important because they clue scientists into the vibrant communities that find a way to live even in remote, hard-to-reach environments.

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Studying the whale graveyards “is important for understanding how life can adapt to such extreme conditions, not only due to the lack of light and oxygen but also to the incredibly high pressure,” said study co-author and paleontologist Giovanni Bianucci with the University of Pisa in Italy in an email.

Ramakrishnan writes for The Associated Press.

The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Department of Science Education and the Robert Wood Johnson Foundation.

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El Niño turns crumbling California pier into climate battleground over what to save — and who pays

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El Niño turns crumbling California pier into climate battleground over what to save — and who pays

As a historic El Niño supercharges the Pacific Ocean and San Francisco experiences record high seasonal sea levels, the latest structural casualty of intense wave action is prompting Bay Area politicians to call for help from the state and federal governments.

They want to rebuild a concrete pier shut down this month after officials deemed it unsafe because of cracking from decades of pounding surf and storms.

As waves crashed against the derelict structure Monday morning, U.S. Rep. Sam Liccardo (D-San José) held a news conference and asked the federal government to follow through on $50 million in climate resilience funding promised by the Biden administration but terminated by the Trump administration in 2025.

The city of Pacifica had been on the shortlist for the Building Resilient Infrastructure and Communities program, managed through FEMA. California and 22 other states successfully sued to reinstate the program, but the funding has yet to be allocated.

Liccardo also asked for nearly $1 million in promised funds from the National Oceanic and Atmospheric Administration for a handrail project on the pier and an additional $9 million to protect coastal bluffs.

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Coastlines are already being buffeted and inundated by rising seas. With the closed-off Pacifica Municipal Pier in the background, local politicians and community members said they’re on the front lines and want to rebuild.

“Pacifica is ground zero for coastal resilience,” said state Sen. Josh Becker (D-Menlo Park), as he asked Gov. Gavin Newsom to declare a state of emergency and “help us fix this pier and help this community recover again.”

“This is very much a reminder that an ounce of prevention is worth a pound of cure,” he said, noting that previous attempts for funding went unheeded. “We cannot wait until infrastructure fails before we invest in protecting it.”

As climate change starts to become expensive, it prompts questions about what to protect and what to abandon.

Chad Nelson, chief executive of the Surfrider Foundation, a coastal environmental advocacy organization, said city piers provide coastal access to people who can’t swim or walk on the beach; they are often popular fishing spots and tend to serve a broad swath of their communities.

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On the flip side, he said, they keep getting beat up by the ocean and costing taxpayers millions of dollars to repair or replace.

In Santa Cruz, a public wharf damaged by storms in 2024 recently reopened after $1.3 million in repairs. In Capitola, a storm-damaged wharf reopened earlier this year after $10 million had been sunk into repairs. The city is now considering building an open-air restaurant, public bathrooms, a bait shop and a boat launch.

“I think the larger question is: Are we subsidizing bad responses to problems that we know are going to persist?” he said, responding to a question about infrastructure that won’t last.

Charles Lester, director of the Ocean and Coastal Policy Center at UC Santa Barbara, agreed with Nelson that it’s important to distinguish public from private benefits.

“There’s a bit of a difference between a public recreational pier, for example, and your private development that’s going to impact the beach,” he said.

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And at some point, he said, we have to acknowledge things are only going to get worse.

In a white paper authored by Lester and Nelson, the two described the coming El Niño as a “reckoning” for the California coast.

El Niños result in larger waves, elevated sea levels and powerful storms — “predictable signature(s) of a climate pattern that returns every two to seven years and is expected, as the planet warms, to intensify,” they wrote.

Wave energy along the shore can run 50% above average during an El Niño, while sea levels can climb 6 to 12 inches — flooding coastal homes, roads and infrastructure. Coastal erosion increases by more than 69% during extreme El Niño events, according to the U.S. Geological Survey.

During the 1997-98 El Niño, seven Pacifica seaside houses were condemned after powerful waves and storms made them unsafe and irreparable. Seventeen people in the state died as a result of the historic flooding and storms.

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The funding requests for the pier also come as San Francisco sees its highest summer water levels ever. On Saturday, the National Weather Service recorded levels 1.83 feet above normal high tide. Early Monday morning, the popular Pier 14 along the city’s Embarcadero waterfront was submerged.

High surf along the coast killed a young girl in Laguna Beach, and hundreds of people have been rescued at Newport Beach. Water stranded a hiker along the cliffs of San Francisco’s Presidio — requiring a seven-hour rescue mission that ultimately left the hiker and a rescuer injured as the waves crashed them into the rocks.

“This stretch of coast has been a continuous coastal emergency declaration for almost 10 years due to the repeat damage of storms in recent El Niño years,” the mayor of Pacifica, Christine Boles, said.

Pacifica has been planning for climate change for years, she said. But climate change is outstripping those efforts, and without financial and regulatory support from the federal and state governments, the battle will be all but lost.

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