Matthew Wilson listens in on rodents’ dreams. Nancy Kanwisher studies a blueberry-sized region in the human brain that specializes in face recognition. Elly Nedivi spies on the comings and goings of brain cells in living mice.
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The three once delved into the workings of the brain from different corners of the MIT campus. But now they’re likely to encounter one another in the five-story atrium or bamboo-lined hallways of MIT’s new Brain and Cognitive Sciences (BCS) Complex, the largest neuroscience research center in the world. When it officially opened its doors in December, Building 46 became home to the Picower Institute for Learning and Memory, the McGovern Institute for Brain Research, and MIT’s Department of Brain and Cognitive Sciences. Once it is full, the 38,000-square-meter building will house more than 40 faculty members and their research groups as well as a state-of-the-art brain-imaging center.
“There is enormous possibility and opportunity” in neuroscience right now, says President Susan Hockfield, a neuroscientist herself. “The study of the brain is the next frontier.” And with so many MIT scientists from different disciplines working under one roof, they’re likely to map new territory that much faster.
“There’ve been tremendous advances in understanding the genetic basis of life and also tremendous advances in brain images,” says Robert Desimone, director of the McGovern Institute. “The challenge for neuroscience is bridging the gap from what goes on inside one cell in your brain to something that through a complex chain results in either normal cognition, thought, language, perception of beauty – or a terrible brain disorder.”
Researchers study the brain at many different levels of analysis; no coherent picture of the brain, from the genome up to what we think of as the mind, exists. The researchers in the Brain and Cognitive Sciences Complex are committed to developing a more complete, nuanced understanding of the brain through interdisciplinary, collaborative research. A typical BCS project might bring a molecular biologist together with a neurophysiologist and a cognitive scientist to study how a neuron’s gene expression is related to the way it sends electrical signals to other cells, and how those signals affect behavior.
By documenting the workings of the normal human brain, scientists in the BCS complex ultimately hope to determine exactly what goes wrong in the brains of people with autism, dyslexia, Alzheimer’s, and other disorders. They’ll also be looking for insights into such things as how children can learn to manage angry emotions and what causes loss of motor control in Parkinson’s disease. Research at the McGovern Institute is wide ranging, with faculty studying habit formation, neurological cancer, touch perception, and more. Picower Institute research focuses on learning and memory. Most researchers in both institutes are professors in the BCS department; some have dual appointments in biology and other departments.
The value of the BCS complex, says Hockfield, is that it “brings these people together so they can share understanding and talk across what in other places might be divisions between departments and distances between buildings. Work in one area can cross-fertilize work in another – and that’s a tremendously important feature of modern science, particularly modern neuroscience.”
To encourage such cross-fertilization, the BCS building was designed with an eye to fostering community. Inside, open corridors arranged around a central atrium flow between the sections of the building housing the McGovern and Picower Institutes and the BCS department. Common areas – including nooks with groups of armchairs and tea rooms with windows looking into the atrium or out to the city – are bathed in inviting natural light even on a cloudy day. Susumu Tonegawa, director of the Picower Institute, says that the abundance of common spaces in the new building is important because “the seeds of great research ideas often originate from casual conversations.” Before moving into the complex, Picower researchers were based in four separate buildings.
To give you a sense of the ideas that are percolating in the BCS complex, here’s a look inside the labs of three BCS scientists whose work puts them on the cutting edge of brain science.
Picower Institute researcher, biology and BCS faculty member
What is sleep’s role in memory formation?
Enter the BCS complex from Vassar Street, and you’ll be greeted by the Picower Institute’s mission statement, chiseled into the white stone wall along the central stairway. Venture up the stairway to Matthew Wilson’s airy, high-ceilinged office and labs, and you’ll see that mission in action. In the device fabrication lab he helped design, Wilson picks up what looks like a very fine silver hair – four delicate electrodes twisted together. He uses groups of these wires to probe into the brains of rats and mice in order to study the role of sleep in memory formation and maintenance.
Neurons communicate by means of electrical signaling, which Wilson’s electrodes monitor. “It’s like we’re listening in on a conversation in a room full of people by lowering a microphone into the room,” he says. Like a microphone, the twist of wires can be moved, “so that when it gets close to the cells we can listen for activity.” Wilson, who has an electrical-engineering background, “listens” to the electrical activity of 50 to 100 cells at a time with an array of about 20 electrodes.
Wilson eavesdrops on neurons in the hippocampus, a structure deep in the mammalian brain that plays an important role in the formation and upkeep of memories, and in part of the neocortex, the area of the brain responsible for activities ranging from motor coördination to conscious thought in humans. His research appears to support the theory that during sleep, memories are edited and transferred from short- to long-term storage.
When rats and mice walk down a familiar path, Wilson has found, groups of neurons in their hippocampi are activated in a particular sequence. In his labs, rats and mice traverse mazes wearing strange crowns of circular electrode arrays. The electrodes reach the rodents’ brains through holes drilled into their skulls; screws on the arrays let Wilson move the electrodes up or down. Long wires connect the arrays to computers that collect data about neural activity, while overhead cameras track the animals’ positions in the mazes. “We can tell where the animal is in the maze just by looking at activity patterns in the hippocampus,” says Wilson. “As the animal moves, the patterns change. It’s sort of like a movie of the animal’s experience.”
Once they know what this “movie” of signaling patterns looks like, Wilson and his colleagues can watch for a rerun while the mouse is sleeping or sitting quietly. They also look for repeats of the pattern in the neocortex. Using his electrodes, Wilson can monitor the “whole process of experiencing the world and turning it into patterns of activity in the brain.” He then looks for changes in activity patterns that suggest the rodents are forming and editing memories. Wilson is also working with Picower Institute director Susumu Tonegawa to identify the genetic basis of the signaling patterns.
Wilson and his lab mates believe that they have identified memory-related activity in almost all stages of sleep. During light sleep, Wilson says, the rodents play back “brief snippets that are much faster than they were experienced – rapid, MTV-like flashes.” He thinks this means the animals are dreaming about recent experiences. In contrast, “during REM [rapid eye movement] sleep, memory seems to be played out in real time,” which he says suggests “revisiting old experiences, comparing things, and trying to synthesize.” Wilson likens the neural activity during light sleep to preliminary sorting through a pile of papers to decide what’s important and what can be trashed, the in-depth playback of REM to “when you put together the information you have into something more usable.” He has also found that when the mice and rats are doing things that don’t require active attention – such as eating – they go into a sleeplike state and “play back what they were just doing.”
Wilson suspects that if he could monitor human brains with electrodes, he would see similar phenomena. “Mice and human brains differ, but the overall structures in the brains are very similar,” he says. “There’s every indication that there’s something similar in humans.” – By Katherine Bourzac, SM ‘04
McGovern Institute investigator and professor of cognitive neuroscience
Is the brain like a Swiss Army knife?
In a sunny, fourth-floor office in the McGovern wing of the BCS complex, Nancy Kanwisher thinks small. Kanwisher ‘80, PhD ‘86, has spent a decade strengthening the case that a blueberry-sized area of the brain is active only when you look at another person’s face. It is not interested in images of apples, trucks, or even other body parts.
“The general emphasis in my lab has largely been to focus on parts of the brain that are very strikingly specialized for one particular cognitive function,” says Kanwisher. In addition to the face response area, she and her colleagues have identified three other brain regions that respond only to images of places, bodies, and written words in almost every person tested.
Kanwisher’s interest has plunged her into a fierce, 200-year-old debate about the human brain. Is the brain like a Swiss Army knife, made up of specialized parts that perform specific tasks? Or is the brain a generalist, able to solve problems on the fly without any customized tools? “Pretty much everyone has agreed for a long time,” Kanwisher says, that the cerebral cortex or higher brain has a motor area that specializes in the mental processes that guide the taking of a step or the shaking of someone else’s hand. But the notion that abstract thought processes – such as guessing what other people are thinking, parsing the syntax of a sentence, or recognizing faces – may have dedicated areas in the brain is much more controversial. “A lot of people in my field prefer to have ideological debates, but I prefer just to stick subjects in the scanner and find out,” Kanwisher says.
In order to stick subjects in a scanner, Kanwisher used to have to commute off campus. “We’ve been lucky to use the scanners at the Martinos Center in Charlestown for the last 10 years,” she says. “But it’s always a nuisance to drive across town and then discover that something’s wrong with one of your computers.” Kanwisher will soon be able to stay within the BCS complex and use the new brain scanner in the Martinos Imaging Center at the McGovern Institute.
To locate regions of the brain specialized for particular tasks, Kanwisher uses functional magnetic resonance imaging (fMRI), which measures neural activity in terms of local blood flow. She initially found the face-specialized region by looking for areas that were more active when subjects looked at faces than when they looked at objects.
Then she had to rule out other possible reasons for the stronger signals. The putative face region might have been wired to respond to round things or to human body parts generally; or it might have been part of an attention-boosting mechanism, which faces activated because social interaction is so crucial for humans. “There are literally dozens of alternative accounts. The signature of my work,” Kanwisher says, “is to take all of these alternative accounts seriously and test them, every one if we can.” This process takes years.
“One of the biggest questions I’d love to answer is where all this structure in the brain comes from,” Kanwisher says. She finds the same specializations in the same brain regions in nearly every single subject she scans. “It’s like the liver or the kidney. They’re just parts of the system.” Are they the result of natural selection, since identifying faces, places, and bodies are such vital human tasks? Or might they be the result of changes in individuals’ brains?
Kanwisher’s recent work with postdoc Chris Baker, which examines a brain structure involved in reading, suggests that experience can train brain regions to respond selectively to different stimuli. When people who read Hebrew look at Hebrew words, for instance, they have twice as strong a response in the written-language area of the brain as people who do not read Hebrew.
Kanwisher doesn’t believe the entire brain is specialized. “I think some domains of [abstract thought] get their own bit of brain and others don’t. The question of why some do and others don’t is a very big, interesting one, and it’ll keep us busy for a long time.” – By Katherine Bourzac, SM ‘04
Picower Institute researcher and BCS assistant professor
How adaptable is the adult brain?
Two floors down from Matthew Wilson, Elly Nedivi is trying to understand how the brain stays flexible. Though the basic circuitry of the human brain is set during gestation and early life, the adult brain can still change: we can learn, remember, and react to new situations. “What we’re interested in is how the brain is able to constantly adapt,” says Nedivi.
In all likelihood, answering that question means explaining how the brain’s neurons subtly adjust synapses – the communication points where one cell meets another – to make connections weaker or stronger. To communicate, neurons generate electrical impulses; electrical activity, in turn, can cause physical changes in neurons. Several years ago, Nedivi’s lab found that creating electrical impulses in the brain rouses 360 different genes into action. This pool of genes, many of which had not previously been described, can offer clues to the brain’s adaptability, or what neuroscientists call “plasticity.”
So far, Nedivi’s research on just two of these “candidate plasticity genes” (CPGs) has shown that the brain can modulate cell communication on many levels. One gene, CPG2, causes the cell to withdraw receptors that respond to incoming signals, reducing its neighbors’ influence on it. Another gene, CPG15, encodes a chemical message that tells neighboring cells to grow and become more communicative. Now, Nedivi says, “we can go back and identify additional genes in [the CPG pool] that might be interesting in different ways” and study how all 360 genes might work together.
Nedivi has started using high-tech imaging to see how neurons adapt. Many of the genes her team identified were known to be involved in giving cells their shape and structure. But little was understood about what, if any, structural changes occur in adult brain cells. Nedivi teamed up with Peter So, an MIT professor of both mechanical and biological engineering, to devise a technique that literally provides a window into the adult mouse brain. The researchers implanted two glass discs a few millimeters in diameter into the scalps of living mice that had been engineered to express a fluorescent protein in some of their brain cells. The discs allowed the researchers to peer into the animals’ brains using a powerful microscope and, with the help of special software, to produce detailed, 3-D pictures of the cells. The team could see small but distinct changes over time, as the treelike branches of the cells grew and retracted.
With this tool, Nedivi says, “We can actually look at the neurons and see what they’re doing. And we can ask if they still do that if the brain is sick.” Nedivi envisions using her technique to look for structural defects in the brains of animals with diseases analogous to Alzheimer’s and Parkinson’s, as well as disorders thought to be caused by faulty synaptic communication, such as addiction and anxiety. And for the first time, researchers can view, in living brains, small-scale changes that are usually only studied in cultured cells. “ ‘Learning’ and ‘memory’ are general terms for something we can measure behaviorally,” Nedivi says. How this complex behavior emerges from tiny cellular events is one of neuro-science’s greatest puzzles. – By Courtney Humphries, SM ‘04
Q&A with President Hockfield
What the BCS complex means for MIT
The first life scientist to lead MIT, President Susan Hockfield has studied brain development and the brain cancer glioma and is a professor of neuroscience in the BCS department. She spoke with TR assistant editor Katherine Bourzac about the promise of the BCS complex and the history of collaboration at MIT.
TR: You often say that one of your goals as president is to encourage interdisciplinary work. How does this apply to the BCS complex?
Susan Hockfield: The boundaries between previously established disciplines are growing fuzzy or disappearing. Scientists in the BCS complex would have been located in separate departments 10 or 20 years ago – a department of psychology, cell biology, physics, perhaps a nuclear science and engineering department. I am very interested in helping people talk across what might formerly have been disciplinary divides. Particularly promising is the area at the convergence of the life sciences and engineering – I think it’s going to be one of the most exciting domains of the coming decades.
TR: What does this new complex mean for the life sciences at MIT, and how does it fit into MIT’s history?
SH: The biologists of the world have long been looking at MIT as a leader in the biological sciences, particularly as the molecular-biology revolution took place, because many of the seminal discoveries were made here at MIT.
I often think about what happened at MIT when President Karl Compton in the 1930s and ’40s insisted that absolutely first-rate activities in the physical sciences needed to be in conversation with engineering. It was possible for him to insist on that because studies in the physical sciences at the beginning of the 20th century brought forward an understanding of the nuts and bolts of the physical universe that could be applied to problems that were going on in the engineering disciplines.
Similarly, studies in the life sciences and biological sciences in the early 1950s and ’60s allowed us to understand life systems at the level of nuts and bolts, and that is now in easy conversation with engineering disciplines. So we see a convergence between the life sciences and engineering that in important ways parallels the convergence between the physical sciences and engineering in the 20th century, which of course produced what we know of as the computer-science revolution. I anticipate that the convergence of the life sciences and engineering will have equally revolutionary results.
The BCS Complex at a Glance
The facility: Located between Main and Vassar Streets, the new Brain and Cognitive Sciences Complex stretches over the railroad tracks dividing north and south campus. The facility includes offices, wet and dry labs, a 30-meter-high atrium, and an advanced imaging center. Take a virtual tour of part of the complex at http://web.mit.edu/mcgovern/html/Who_We_Are/building.shtml.
The architects: Lead designer Charles Correa, MAR ‘55, collaborated with the firm Goody, Clancy, and Associates, which designed the labs and research spaces.
The price tag: The $175 million facility was funded in part by portions of two exceptional gifts: the 2002 Picower Foundation donation of $50 million (the largest ever made to MIT from a private foundation) and the gift of $350 million from Lore and Pat McGovern ‘59 in 2000 to establish the McGovern Institute (the largest donation of any kind in MIT’s history).