Understanding the Brain's "Brake Pedal" in Neural Plasticity

You definitely want to avoid an encounter with a banded krait. A single bite from this snake delivers enough venom to spell the end for a dozen people. Working like a chemical brake, the active toxin finds its way to your neurons, and snuffs out the signals that would otherwise animate your muscles. It’s bad stuff.

Which makes it all the more surprising that the venom, or something very close, is found in our heads. Recent work from Professor Takao Hensch’s Harvard lab shows that a close molecular cousin of the krait’s toxin, called Lynx1, serves as a kind of brake in the brain. Rather than silencing neurons outright, molecules like Lynx1 help hold them in check, suppressing their tendency to grow and otherwise change with experience. In the absence of these brakes, our brains’ circuits are sprawling and adaptable, but also somewhat unstable.

When we are young, we live through a biological “critical period” -- a time when there is little braking, and the brain is extraordinarily adaptable. Certain kinds of learning seem to just happen without much special attention or practice. None of us learned our native tongue by memorizing rules and exceptions for juggling different parts of speech. Instead, our brains seemed somehow ready for the necessary information, and the information found its way in.

As the brain ages, it is much less willing to meet the world halfway. Instead of easily re-molding itself to accommodate new kinds of inputs, the older brain is more constrained - a biological truth known to anyone who’s struggled to pick up a new language later in life. While many processes contribute to this change in the brain’s learning potential, scientists believe that some of the changes are brought about by the gradual accumulation of molecules, like Lynx1, that limit the brain’s adaptability.

Of course, it might seem like a raw deal to be ‘bitten’ by your own brain, and have your neural prowess slowly snuffed out. But in fact, this is the necessary - if less exciting - second half of a process that stores knowledge in a format that’s accessible for life. Without some kind of insulation from change, the youthful neuronal clay would never set, making life’s lessons unstable and prone to degrade. So although Lynx1 and other molecules cut off our critical period by hitting the brakes on plasticity, they also help lock in knowledge for the long term.

Naturally, scientists have long been interested (reviewed here) in understanding the specifics of how these brakes work, and, perhaps one day, how to control them. With their investigation of Lynx1, the Hensch group has found what may be one of the major factors responsible for closing the door on plasticity after the critical period. In addition, they demonstrate a strategy for lifting the brake to enhance adult plasticity and repair wiring errors in the brain. This could have major implications for the treatment of developmental disorders and brain injuries, and may eventually provide ways to augment cognition in later life.

The first step in investigating Lynx1’s properties was to ask if it accumulated at the right time to function as a plasticity brake. By labeling and collecting samples of Lynx1 and its precursors from the brains of mice at different ages, the researchers tracked how its levels changed over time. Its concentration was low and steady at young ages - within the known critical period for mice -- and ramped up with age.

Of course, many molecules are expected change their concentration over the critical period, and many of them could be just going along for the ride without playing a role in critical period closure. If Lynx1 really was a brake, then letting up on it should enhance plasticity in older brains.

Using genetic engineering techniques, Hensch’s group went a step further -- they removed this brake in mice, and asked if their brains were still plastic past the usual critical period. Could these older brains be rewired by experience, in the manner usually seen only in young brains? To answer this, Dr. Hensch and his colleagues modified a classic experimental paradigm developed by Drs. David Hubel and Torsten Wiesel - the Nobel prize winning duo who did foundational work on the neurobiology of critical periods in the visual system.

The basic experimental approach is to record from neurons of the visual cortex of an animal - in this case a mouse - some time after one of its eyes has been sutured shut. As you might expect, depriving the visual cortex of half of its expected input is a major change in experience that can trigger changes in brain organization. Over time, more neural real estate is devoted to handling inputs from the good eye, at the expense of the bad eye. This is known as a change in “ocular dominance.”

The team found that, unlike control mice, which only undergo ocular dominance shifts if an eye is closed early in life, mice without Lynx1 still showed these shifts for eye manipulations well into adulthood. Thus, an old brain without Lynx1 is still plastic, as if the critical period had never closed. In another experiment, the group also showed that a brain without Lynx1 was also more adept at repairing itself.

While genetically eliminating Lynx1 is a sure-fire way to promote plasticity, this is unlikely to ever be the basis of ‘plasticity therapy’ in humans. Practically speaking, we can’t be re-engineered to lack Lynx1. However, another way of getting at a similar end - and one with more potential as a therapy - is to find out what the plasticity brake is acting on, and try to artificially boost the process being suppressed.

Using pharmacological and molecular labeling studies, Hensch and his colleagues found that Lynx1 works by blocking receptors for the neurotransmitter acetylcholine. Acetylcholine is infused broadly throughout the brain during intense concentration or arousal, and essentially delivers a wake up call to neurons that can prompt them to change their response properties and physical organization. By deafening neurons to these alerts, Lynx1 effectively cuts off the brain’s ability to change.

At the same time, this suggests that plasticity in later life can be enhanced by delivering drugs that boost acetylcholine levels. Indeed, Dr. Hensch’s group found that infusions of drugs that raise acetylcholine could make the mice’s brains more adaptable.

Although directly applying this to humans is probably still a ways off, it raises certain tantalizing possibilities. Naturally, most thoughts turn to some kind of ‘brain boosting’ that would help us learn certain kinds of skills with the same ease we enjoyed when we were younger. Who wouldn’t want a bit more neuro-mojo, or to be able to soak up a handful of new languages just by casually hanging out in countries we’ve always wanted to visit?

It’s not clear, though, that removing Lynx1 would necessarily spell happy times for learning complex skills and languages. These may be subject to additional, or simply different forms of regulation. Still, this research might also help with more immediate, if more modest, goals. It may be possible, for example, to use acetylcholine boosters to increase the effectiveness of brain training programs for staving off senescence and cognitive decline with age.

Mental Blizzard

Turkish novelist and 2006 Nobel laureate Orhan Pamuk found inspiration from daydreams for works such as Snow (2004, Knopf). In a speech titled “the Implied Author” that Pamuk gave when he received the Puterbaugh literary prize in 2006 , Pamuk declared: "I long for inspiration to come to me (as poems did to Coleridge—and to Ka, Snow's hero) in dramatic ways, preferably in scenes and situations that might sit well in a novel. If I wait patiently and attentively, my dream comes true. To write a novel is to be open to these desires, winds and inspirations, and also to the dark recesses of our minds and their moments of mist and stillness.

For what is a novel but a story that fills its sails with these winds, that answers and builds upon inspirations that blow in from unknown quarters, and seizes upon all the daydreams we've invented for our diversion, bringing them together into a meaningful whole?"

Willi Dansgaard in Memoriam

Willi Dansgaard, the great Danish paleoclimatologist, died on January 8. His passing has received remarkably little notice in the world press, though the New York Times published an appreciative obituary today. Were there a Nobel Prize in the earth sciences, he surely would have been a recipient. As it was he had to content himself with the Tyler Prize, the highest award given for environmental research, which he shared with Hans Oeschger, the Swiss glaciologist with whom his work was closely linked, and Claude Lorius, a French scientist.

It was Dansgaard who discovered that the temperature of the earth's atmosphere could be inferred from the isotopic composition of rainwater and snow, and who then realized that the past temperatures of the atmosphere could be extracted from ice cores. Oeschger made himself the world's foremost expert on the measurement of carbon dioxide and other gases found in ice cores. Their work led eventually to a complete year-by-year reconstruction of the earth's climate going back a million years, through a handful of ice ages, showing a powerful linear relationship between greenhouse gas levels and temperatures. Lorius led a team that produced an early version of that record, going back hundreds of thousands of years, based on drilling in Antarctica.

Dansgaard and Oeschger also discovered cycles in which drastic climate changes were found to occur much more rapidly than anybody had imagined--on the scale of decades, rather than hundreds or thousands of years. Though Dansgaard was a rather apolitical person, the discovery of abrupt climate change put it on the global agenda, leading to language in the Rio Framework Convention on Climate Change calling for measures to prevent "dangerous" climate change.

It's regrettable that we don't have a Nobel prize in the geosciences, and not merely for personal reasons. There's altogether too little appreciation of the fact that a revolution occurred in the earth sciences in the second half of the twentieth century, as science historian Spencer Weart has observed, and that the study of the biosphere remains one of the most dynamic of the physical sciences today. Yet earlier this week the Washington Post published an excellent article detailing how most of the major U.S. satellites dedicated to monitoring changes on the Earth's surface and in its atmosphere are behind schedule and under-funded. These include the Global Precipitation Measurement mission, the latest Landsat satellite, Hydros, and the NPOESS satellite set.

Fourteen Actors Acting

here

People

Tani Ikeda
Sex-Ed Trendsetter
For many of us, sex education consisted of half-truths whispered in the school cafeteria or movies in health class that suggested abstinence and heterosexuality were our only options. In 2009 Tani Ikeda, a new graduate of the University of Southern California (USC) film program, posed the question What would happen if young women took sexual health education into their own hands? Read more>>

Rebecca Solnit
The Silver Cloud
In the immediate aftermath of Hurricane Katrina, media outlets too often portrayed survivors as helpless victims or barbaric looters, not only propagating public fear and panic but also painting a distorted portrait of disaster-stricken areas. When an earthquake devastated Haiti five years later, reporters followed the same narrative thread. Activist and author Rebecca Solnit is telling a different story, a story of strength and resilience. Read more>>

Kieran Egan
Teacher of the Years
The curriculum for K-12 education looks like a vast encyclopedia of human knowledge, notes Kieran Egan, a professor of educational theory at British Columbia’s Simon Fraser University. Unfortunately, the information students learn often fades away after only a few years—even if they manage to do well on tests. He posits that this is a result of an education system that values breadth over depth. In his new bookLearning in Depth, Egan offers a solution, arguing for an ambitious but simple change in curriculum. Read more>>

Anil Gupta
Intellectual Pollinator
When it comes to developing the technical infrastructure of the 21st century, economists tend to look to upscale R&D labs, high-tech universities, and big-buck venture capitalists. Business professor Anil Gupta has a radically different vision, one he calls G2G, or “grassroots to global.” Read more>>

Woody Tasch
Free-Range Capitalist
Woody Tasch believes that local, sustainable food is a good investment: in our communities, our land, our health, and, if all goes well, our pocketbooks. Tasch is the founder of the Slow Money Alliance, which aims to get a million Americans to invest 1 percent of their assets in local food systems in the next decade. Read more>>

Nina Dudnik
A Scientist’s Scientist
Every year, U.S. research facilities spend billions on equipment—and dump last year’s models in the landfill. Many of the castoffs are perfectly usable, according to Nina Dudnik. “Equipment upgrades are not so much key functionalities as bells and whistles,” she says. Meanwhile, university labs in developing nations are starved for basic equipment. As a student at Harvard University, Dudnik founded Seeding Labs to address the disparity. Read more>>

Natalia Allen
Conscientious Fashionista
More than 8,000 chemicals were used to make the clothes in your closet. Approximately 1,800 gallons of fresh water were used to manufacture the jeans you’re wearing right now. All-too-commonplace numbers like these make it clear that the fashion industry needs an eco-makeover. Natalia Allen is up for the challenge. Read more>>

Judith Butler
War Empathizer
In 2004 Americans gaped in shame and anger at images of nude, hooded prisoners heaped on top of one another, menaced with dogs or forced to masturbate by members of the U.S. armed forces at Abu Ghraib prison in Iraq. Major media outlets soon settled on an angle for the story: Those responsible for the abuse—keen to exploit Islamic taboos on public nudity and homosexuality—cruelly crafted methods of torture to disgrace conservative Muslims. In her recent book Frames of War: When Is Life Grievable? philosopher and gender theorist Judith Butler retells this story but boldly revises the conclusion. Read more>>

Annette Rizzo
Judge Advocate
At the beginning of 2010, about 10 percent of all U.S. home owners with a mortgage were at least one month behind on payments, according to statistics compiled by the Mortgage Bankers Association, with the percentages far higher in some counties and among subprime mortgage holders. And the number of new foreclosures remains roughly double the rate of five years ago, according to the New York Federal Reserve. All of this serves as a backdrop to a successful foreclosure diversion program launched in 2008 and led by Annette Rizzo, a judge in Philadelphia’s Court of Common Pleas. Read more>>

Perry Chen
The Virtual Patron
Creative artists typically have just three methods for funding projects: They can attempt to infiltrate the marketplace through gatekeepers like galleries, publishers, or recording labels; they can appeal to nonprofits and foundations that superimpose their own agendas on artistic goals; or they can wait tables. With Kickstarter, Perry Chen envisions a fourth paradigm. The idea is simple: Artists pitch their idea with a video on the Kickstarter website. Read more>>

Michelle Ajamian and Brandon Jaeger
Local Food Lovers
Excited about the burgeoning local foods movement, Michelle Ajamian and Brandon Jaeger took a close look at the food they ate. To figure out how to build a regional system for staple foods—including storage and transportation—Ajamian and Jaeger established the Appalachian Staple Foods Collaborative in 2008. This year they opened Shagbark Seed and Mill, a prototype processing facility, at the Appalachian Center for Economic Networks in Athens. Read more>>

Elinor Ostrom
The Commoner
Sharing is one of the first things we learn as small children, yet capitalism suggests that we set it aside as a naive notion: It’s every man for himself.Elinor Ostrom is one of the first social scientists to specifically study the things we share—from oceans and forests to roads and money systems—and breathe fresh life into an old term: the commons. Read more>>

Her Body, Their Chemicals

A scientist, poet, and cancer survivor, Steingraber makes a passionate and lyrical case for eliminating carcinogens, which are ubiquitous in our environment. A movie based on her book Living Downstream was released in spring 2010. Read more>>

Ted Howard

Workers’ Advocate

Instead of reheating failed job-creation strategies like tax breaks for corporations, Howard’s Democracy Collaborative helps low-income workers build democratic, worker-owned companies that offer living-wage jobs in America’s depressed cities—and a personal stake in America’s future. Read more>>

Rebecca Onie
Home Health Advocate

MacArthur “genius award” winner Onie runs Project HEALTH, which enlists college students, many pre-med, as volunteer social workers who connect low-income people to housing, heating assistance, and other nonmedical resources vital to health. Read more>>

Elizabeth Scharpf
Essential Entrepreneur

A simple lack of menstrual pads keeps many women and girls in developing nations home from work and school. Scharpf’s Sustainable Health Enterprises supports entrepreneurs in Rwanda and other countries in devising sustainable pads. Read more>>

Alexander Petroff
Sustainability Trainer

Petroff’s Working Villages International provides support and know-how to economically and environmentally sustainable practices in developing countries. Four years into the project, the model village of Ruzizi, Congo, supplies the region with organic produce. Read more>>

Glen Barry
Eco–Rabble Rouser

An early political blogger, Barry has built a massive network for ecological change. His “global grassroots advocacy” adds muscle to local environmental fights all over the planet, and when mainstream green groups fall short, he speaks up. Read more>>

Paul Ewald
Virally Minded

Biologist Ewald researches the link between infections and cancers, hypothesizing that, as in cervical and liver cancer, there’s a causal link between viruses and other forms of the deadly disease. His radical hypothesis: Simply preventing the spread of viral infection could lead to a lasting cure. Read more>>

Tim Wise
The Confrontationalist

The promise of a post-racial society is premature, Wise argues in his book Colorblind. This activist, who cut his teeth on the campus-based antiapartheid movement, observes that because race is still a key factor in American disparities, economic and otherwise, it demands head-on confrontation. Read more>>

Bryan Doerries

Ancient Healer

Sophocles’ tragedies explore the mental scars of battle. Under a U.S. Defense Department contract, Doerries’ Theater of War brings them to life for modern soldiers and their families to facilitate healing discussions about deep-seated war wounds. Read more>>

Victoria Pettibone and Sasha Eden
Dramatic Opportunists

Women writers, directors, and producers are grossly underrepresented in film and theater; Pettibone and Eden established the organization WET Productions to advance women in the industry and to challenge stereotypes.Read more>>

Bill McKibben

Voice of Reason, Man of Action

Bill McKibben basically invented the job title “climate change expert”: He wrote the first general-audience book on the subject back in 1989. Since then, he has continued to draw awareness to the predicament in a prodigious stream of books, articles, and media appearances, always coming off as reasoned and authoritative even when climate-change deniers attempt to paint those who bring this message as unhinged and alarmist. Read more>>

Alex Gibney: The Smartest Guy in the Room

“If you’re entertaining people, you can say almost anything you want,” declares documentarian Alex Gibney, offering an aptly playful description of his hard-hitting, info-jammed, message-minded cinema. From Enron: The Smartest Guys in the Room (2005) through this year’s Casino Jack and the United States of Money and the new Client 9: The Rise and Fall of Eliot Spitzer, Gibney coats his bitter pills with the sugar of dark comedy, as the men too big to fail—the men in whom we ordinary schmoes invest our trust, if not our cash—inevitably slip on banana peels.

In the eye-popping visual vocabulary of Client 9, for instance, Gibney likens Spitzer, the former New York governor turned sex scandal pariah, to a leopard on the prowl—scary and sympathetic, hungry and vulnerable.

What makes Gibney unique in this era of rampant first-person documentary is that, without his actual presence on screen ingratiating him with the viewer, the director nonetheless establishes an authorial personality as big as Michael Moore’s. His storytelling is uncommonly cinematic among documentary makers, and his themes are fall-of-Rome epic, more anthropological than psychological.

“You can see in my films that I get worked up about abuses of power and authority,” says Gibney. “Most corrupt individuals get away with their crimes by saying ‘trust me’—like the Enron guys, for instance. You act regal and you’re not questioned.”

Questioning the unquestionable has been Gibney’s stock-in-trade for longer than the 10 years he has been directing nonfiction films. His gifts as an interviewer stem not from his tenure at UCLA film school, he says, but from his childhood.

“My mom was a wild character, something of a writer; my dad was a journalist; and my stepdad was a political activist,” he says. “They encouraged me to be curious, to ask tough questions and not to kneel before authority.”

Perhaps on the strength of his past work, including the unusually somber Oscar-winning Taxi to the Dark Side(2007), Gibney persuaded Spitzer to allow himself to be grilled in Client 9 to a degree that the politician has never before experienced, not even under the hot lights of scandalmania.

“It was hard for him to sit for some of those questions about his involvement in prostitution, because it meant having to confront some stuff that I’m not sure he’s ever properly confronted,” Gibney says. “He was reckoning with those questions, though, in a way he couldn’t fully articulate or even understand.”

Believe it or not, Client 9 and Casino Jack, a typically cockeyed look at disgraced überlobbyist Jack Abramoff, constitute less than half of Gibney’s recent and upcoming work. He directed My Trip to Al-Qaeda, which premiered on HBO in September. He shot one chapter (the best one, incidentally) of the bookFreakonomics, newly released to theaters after a run on cable. Nearly completed are Gibney’s feature-length documentary portraits of writer Ken Kesey and bicyclist Lance Armstrong.

“It does become all-consuming sometimes—much to the chagrin of my family,” the filmmaker says. “Sometimes I feel I should be committed.”

Does that mean the documentarian’s life resembles that of Spitzer, a self-described “relentless” prosecutor?

“It does to some extent, yes,” he confesses. “Just don’t tell my wife about the hookers.”

There again is the essence of Gibney: Entertain your audience and you can say almost anything you want.

Extras:

Read a New York Times profile of Alex Gibney; read Gibney’s blog for The Atlantic, where he writes about subjects including politics, human rights, and the arts; and see the trailer for Client 9: The Rise and Fall of Eliot Spitzer.

Julian Assange: The Sunshine Kid

A grainy black-and-white video tracks a group of men who scatter in a cloud of dust to a soundtrack of gunshots. “Keep shooting,” a voice repeats calmly. “Keep shooting.” On the video, the Apache helicopter gunmen obey, until most of the men lie dead in the street. A van pulls up in an attempt to remove an injured man from the scene. The gunmen blow up the van.

The official response: Just another afternoon of Operation Iraqi Freedom.

It’s likely that the 2007 incident wouldn’t have registered more than a blip in the nightly news except that two of the men killed were a Reuters photographer and his assistant. (The American helicopter crew mistook the camera for a weapon.) Even so, the chilling video footage of the incident would remain classified except for the extraordinary efforts of the website WikiLeaks.

Launched in 2007, WikiLeaks publishes classified documents—like the Apache helicopter video film of the shooting of the Reuters newsmen—that would otherwise never see the light of day. The volume of leaks on the website is overwhelming. Notable among them are Sarah Palin’s hacked e-mail messages, a banned report on assassinations and torture enacted by Kenyan police, and tens of thousands of classified documents related to the war in Afghanistan.

A notorious Australian ex-hacker, Julian Assange is only one of a dozen, mostly anonymous, people who helped set up the site, but he’s become the face of WikiLeaks and a tireless proponent of exposing the ruling class’s dirty secrets. “It is impossible to correct abuses,” Assange told the Oslo Freedom Forum in 2010, “unless we know that they’re going on.”

The rise of WikiLeaks comes at a crucial time, when daily and alternative newspapers—the traditional vehicles for exposing wrongdoing in government and business—are gutting newsrooms, disassembling costly investigative teams, and refocusing on profit. “When I look at the next ten years, investigative reporting is going to die in corporate settings,” Nick Penniman of the Huffington Post Investigative Fund recently toldColumbia Journalism Review.

WikiLeaks represents a ray of sunshine. By placing raw documents in the public domain, the organization not only leaps past the interpretive and gatekeeping roles of investigative reporting but also subverts the power of governments and businesses to censor the paper trail of their actions. (Reuters filed a Freedom of Information Act request for the video that captured the shootings of its newsmen. The request was denied. WikiLeaks never asked for permission in the first place.)

Predictably, the first wave of reaction from U.S. officialdom has been righteous outrage. Bradley Manning, the Army intelligence analyst who reportedly leaked the video and other documents, has been arrested. Assange leads a semi-clandestine existence, avoiding the United States, where he could conceivably be arrested.

The New Yorker’s Raffi Khatchadourian recently blogged about the foolishness of the official response, likening it to music industry attempts to shut down file sharing. “The government has its own versions of WikiLeaks: the Freedom of Information Act,” he writes. “An official government Web site that would make the implementation of FOIA quicker and more uniform, comprehensive, and accessible, and that might even allow anonymous whistleblowers within federal agencies to post internal materials, after a process of review and redaction, could be a very good thing—for the public, and for the official keepers of secrets, too.”

Extras:

Despite the roguishly idyllic, anonymous digi-world of government transparency offered by WikiLeaks, Julian Assange is himself a mysterious character—when you piss off international governments, Swiss banks, and touchy religious groups it’s best to keep a low profile. After exposing covered-up injustice on a global scale, Assange has become a globetrotter, working in Kenya and Iceland, Washington, D.C. and his native Australia. Mother Jones’s David Kushner profiled Assange and criticized the tactics of WikiLeaks, enraging the hacktivist enough to call the muckraking magazine a “right-wing reality distortion field.” Regardless, if you want to know when Sarah Palin’s e-mail account is hacked again, follow the WikiLeaksTwitter and Facebook accounts.