News / Science & Technology

See-Through Brains Promise to Clear Up Mental Mysteries

A three-dimensional rendering of clarified brain (Courtesy of the Deisseroth lab)
A three-dimensional rendering of clarified brain (Courtesy of the Deisseroth lab)
Reuters
If Dr. Karl Deisseroth were an architect, he might be replacing stone or brick walls with floor-to-ceiling glass to build transparent houses. But since he is a neuroscientist at Stanford University, he has done the biological equivalent: invented a technique to make brains transparent, a breakthrough that should give researchers a truer picture of the pathways underlying both normal mental function and neurological illnesses from autism to Alzheimer's. In fact, the first human brain the scientists clarified came from someone with autism.
       
Deisseroth and his colleagues reported in the online edition of the journal Nature on Wednesday that they had developed a way to replace the opaque tissue in brains (harvested from lab mice or donated by people for research) with "hydrogel,'' a substance similar to that used for contact lenses.
       
The result is see-through brains, their innards revealed in a way no current technique can: Large structures such as the hippocampus show up with the clarity of organs in a transparent fish, and even neural circuits and individual cells are visible.
       
The announcement comes just a week after President Barack Obama announced a $100 million initiative to plumb the mysteries of the brain, and offers hope that at least some of the technological breakthroughs the project envisions are within reach.
       
Neuroscientist William Newsome, who will co-lead Obama's initiative, called the hydrogel technique "a major technological innovation'' that "will speed our mapping of the brain's 'circuit diagram.''' That mapping, he said, is "an essential goal of neuroscience, and will probably be a substantial focus'' of Obama's brain project.
       
Until now, the only way to trace neural connections was by cutting a brain into ultra-thin slices, examining each slide under a microscope to map the cells and then using a computer to virtually reassemble the slices to reveal the entire circuit.
       
But slicing the brain like so much salami deforms the tissue and makes it difficult to work out long-range connections, like those between such far-flung regions as the prefrontal cortex and the amygdale.
       
Neuroscientists have therefore long dreamed of studying intact brains, said Deisseroth: "That would give you a better chance of working out connections over large distances, which would help you determine structure-function relationships.''
   
Circuitry and Synapses
       
Deisseroth's process, dubbed CLARITY (an anagram for the technique), works by a delicate feat of biochemical engineering. It turns out that what makes the brain opaque are the fatty membranes that surround and support its cells. Removing these layers by brute force, however, would make the brain tissue collapse in a puddle of neuro-glop.
       
Instead, Deisseroth and his colleagues immersed the brains of three-month-old mice in a vat of soft, jelly-like hydrogel. Molecules of the hydrogel seeped into the brain and took the place of the lipid bilayers, which were then removed through an electro-chemical process.
       

Once the hydrogel was in place, the scientists heated it to just above body temperature, causing the molecules to connect to one another and form a sturdy mesh that acted like a shell holding in the contents of each brain. After eight days, the scientists had just what they had hoped for: an intact, see-through mouse brain.

CLARITY "is a giant step forward from having to slice the mouse brain into 1,000 pieces and looking at them each individually, then trying to reconstruct the relationships of all those slices,'' said neuroscientist Cori Bargmann of Rockefeller University, also a co-leader of Obama's brain initiative. Because neural connections can be mapped in an intact brain, she said, "I think it will accelerate research in neuroscience.''
       
The Stanford scientists could see the thalamus and the brainstem, the cortex and hippocampus with the naked eye. Using a microscope revealed the white matter that serves as a brain's transmission lines, carrying signals from one neuron to another in far-flung circuits that underlie mental function.
       
The scientists posted a three-dimensional tour of the transparent mouse brain on YouTube.      


Crucially, the hydrogel is not only transparent but also permeable. That allows scientists to infuse into the brain special fluorescent dyes and other molecules that attach to just one of the thousands of different kinds of brain cells, and even to individual proteins and other molecules, turning the circuitry a neuroscientist wants to study into chartreuse and other can't-miss hues when viewed in special light.
       
"You can paint different wires different colors,'' said Deisseroth, who is one of 15 experts on the team that will map out goals for Obama's brain initiative. "We could see structures down to paired neurons on each side of a synapse,'' the neural version of seeing that the toe bone is connected to the foot bone and the foot bone to the ankle bone.
       
Perhaps even more remarkably, the process worked on human brains, despite concerns that the use of preservatives like formalin or formaldehyde might block the hydrogel process. Mouse brains are studied fresh.
       
The scientists clarified one healthy human brain and one autistic brain. Even though the latter had been pickled for more than six years, it took to the new method, revealing numerous "dendritic bridges,'' ladderlike connections within the brain's white matter that resemble those in Down syndrome.
       
"CLARITY has the potential to unmask fine details of brains from people with brain disorders without losing larger-scale circuit perspective,'' said Dr Francis Collins, director of the National Institutes of Health, which helped fund the research.
       
Once other scientists begin to clarify brains, it could "transform the way we study the brain's anatomy and how disease changes it,'' said Dr Thomas Insel, director of the National Institute of Mental Health. "The in-depth study of our most important three-dimensional organ'' will no longer be "constrained by two-dimensional methods,'' and the black box that is the brain could become downright luminous.

You May Like

Photogallery Americans Celebrate Thanksgiving With Feasts, Festivities

Holiday traditions include turkey dinners, 'turkey trots,' American-style football and New York parade with giant balloons More

Video For Obama, Ferguson Violence is a Personal Issue

With two years left in term, analysts say, president has less to lose by taking conversation on race further More

Video Italian Espresso Expands Into Space

When Italian astronaut Samantha Cristoforetti headed for the ISS, her countrymen worried how she would survive six months drinking only instant coffee More

Featured Videos

Your JavaScript is turned off or you have an old version of Adobe's Flash Player. Get the latest Flash player.
South Africa Sees Male Circumcision as Way to Reduce HIV Infectionsi
X
November 28, 2014 3:31 PM
South Africa remains plagued by AIDS despite massive government and NGO efforts on prevention and life-sustaining Anti-Retro-Viral programs. But the country has opened up another front to reduce new HIV infections: promoting circumcision. Emilie Iob reports for VOA News from a pioneering circumcision center in Orange Farm, Johannesburg.
Video

Video South Africa Sees Male Circumcision as Way to Reduce HIV Infections

South Africa remains plagued by AIDS despite massive government and NGO efforts on prevention and life-sustaining Anti-Retro-Viral programs. But the country has opened up another front to reduce new HIV infections: promoting circumcision. Emilie Iob reports for VOA News from a pioneering circumcision center in Orange Farm, Johannesburg.
Video

Video To Make A Living, Nairobi Street Vendors Face Legal Hurdles, Physical Violence

The Nairobi City Council has been accused of brutality in dealing with hawkers in the Central Business District - in order to stop them from illegally selling their wares on the streets. Lenny Ruvaga has more for VOA News from the Kenyan capital.
Video

Video For Obama, Ferguson Violence is a Personal Issue

Throughout the crisis in Ferguson, Missouri, President Barack Obama has urged calm, restraint and respect for the rule of law. But the events in Ferguson have prompted him to call — more openly than he has before — for profound changes to end the racism and distrust that he believes still exists between whites and blacks in the United States. VOA White House correspondent Luis Ramirez reports.
Video

Video Online Magazine Gets Kids Discussing Big Questions

Teen culture in America is often criticized for being superficial. But an online magazine has been encouraging some teenagers to explore deeper issues, and rewarding their efforts. VOA religion reporter Jerome Socolovsky went to this year’s Kidspirit awards ceremony in New York.
Video

Video US Community Kicks Off Thanksgiving With Parade

Thursday is Thanksgiving in the United States, a holiday whose roots go back to the country's earliest days as a British colony. One way Americans celebrate the occasion is with parades. Anush Avetisyan takes us to one such event on the day before Thanksgiving near Washington, where a community's diversity is on display. Joy Wagner narrates
Video

Video Aung San Suu Kyi: Myanmar Opposition to Keep Pushing for Constitutional Change

Myanmar opposition leader Aung San Suu Kyi says she and her supporters will continue pushing to amend a constitutional clause that bars her from running for president next year. VOA's Than Lwin Htun reports from the capital Naypyitaw in this report narrated by Colin Lovett.
Video

Video Mali Attempts to Shut Down Ebola Transmission Chain

Senegal and Nigeria were able to stop small Ebola outbreaks by closely monitoring those who had contact with the sick person and quickly isolating anyone with symptoms. Mali is now scrambling to do the same. VOA’s Anne Look reports from Mali on what the country is doing to shut down the chain of transmission.
Video

Video Ukraine Marks Anniversary of Deadly 1930s Famine

During a commemoration for millions who died of starvation in Ukraine in the early 1930s, President Petro Poroshenko lashed out at Soviet-era totalitarianism for causing the deaths and accused today’s Russian-backed rebels in the east of using similar tactics. VOA’s Daniel Shearf reports from Kyiv.
Video

Video Hong Kong Protests at a Crossroads

New public opinion polls in Hong Kong indicate declining support for pro-democracy demonstrations after weeks of street protests. VOA’s Bill Ide in Guangzhou and Pros Laput in Hong Kong spoke with protesters and observers about whether demonstrators have been too aggressive in pushing for change.
Video

Video US Immigration Relief Imminent for Mixed-Status Families

Tens of thousands of undocumented immigrants in the Washington, D.C., area may benefit from a controversial presidential order announced this week. It's not a path to citizenship, as some activists hoped. But it will allow more immigrants who arrived as children or who have citizen children, to avoid deportation and work legally. VOA's Victoria Macchi talks with one young man who benefited from an earlier presidential order, and whose parents may now benefit after years of living in fear.
Video

Video New Skateboard Defies Gravity

A futuristic dream only a couple of decades ago, the hoverboard – a skateboard that floats above the ground - has finally been made possible. While still not ready for mass production, it promises to become a cool mode of transport... at least over some surfaces. VOA’s George Putic reports.
Video

Video Falling Gas Prices Impact US Oil Extraction

With the price of oil now less than $80 a barrel, motorists throughout the United States are benefiting from gas prices below $3 a gallon. But as VOA’s Kane Farabaugh reports, the decreasing price of petroleum has a downside for the hydraulic fracturing industry in the United States.

All About America

AppleAndroid