McGovern Faculty Portraits

The McGovern Institute faculty comprises one of the most distinguished groups of brain researchers anywhere in the world. Its members include one Nobel laureate, five members of the National Academy of Sciences, and leading experts in many areas of neuroscience.

The Institute currently has 18 principal investigators. Along with its 16 full members, these include two associate faculty members, who collaborate closely with the full investigators and participate in all the Institute’s activities. All McGovern faculty hold appointments in one or more academic departments at MIT.

 

Seeing the light: Ed Boyden’s tools for hackers

The November 2012 issue of Wired UK features McGovern neuroscientist, Ed Boyden.

“Ed Boyden, an engineer turned neuroscientist, makes tools for brain hackers. In his lab at MIT, he’s built a robot that can capture individual neurons and uses light potentially to control major diseases — all in his quest to ‘solve the brain’.” — Ed Yong, Wired UK

Read the full profile here.

 

 

A view of the brain

Magnetic resonance imaging (MRI) provides researchers with a non-invasive method for viewing the human brain in high resolution. This video shows a structural MRI produced at the Martinos Imaging Center at MIT, a state-of-the-art brain imaging facility that serves the biomedical research community at MIT and throughout the Boston area. Video: Christina Triantafyllou

In His Own Words: Joel Z. Leibo

The Friends of the McGovern Institute Student Fellowship has been awarded to Joel Leibo for his work in Prof. Tomaso Poggio’s lab. Leibo’s research asks two key questions: How do we learn to recognize faces? And how can we build machines to do the same? He is applying his background in neuroscience and mathematics to the study of computational models of vision. Leibo plans to use the McGovern Institute’s newly acquired magnetoencephalography (MEG) scanner to decode face-related activity in the human brain.

Welcome to the McGovern Institute

This award-winning video provides viewers with an intimate tour of the McGovern Institute and it explores the tools our researchers are using to unlock the mystery of the human brain. It shows how our research is pushing the frontiers of technology and providing new insights into brain disorders such as autism, Parkinson’s disease, and mental illness.

Produced by Emmy nominated John Rubin Productions, “Welcome to the McGovern Institute” won a 2010 CINE Golden Eagle Award and a 2010 Telly Award, which honors “outstanding local, regional, and cable TV commercials and programs, the finest video and film productions, and online film and video.”

Brain Scan Cover Image: Summer 2012

Neurons in the mouse cerebellum, expressing the synaptic protein SAPAP-4.
Image: Louis Tee and Guoping Feng

How the brain controls our habits

Habits are behaviors wired so deeply in our brains that we perform them automatically. This allows you to follow the same route to work every day without thinking about it, liberating your brain to ponder other things, such as what to make for dinner.

However, the brain’s executive command center does not completely relinquish control of habitual behavior. A new study from MIT neuroscientists has found that a small region of the brain’s prefrontal cortex, where most thought and planning occurs, is responsible for moment-by-moment control of which habits are switched on at a given time.

“We’ve always thought – and I still do – that the value of a habit is you don’t have to think about it. It frees up your brain to do other things,” says Institute Professor Ann Graybiel, a member of the McGovern Institute for Brain Research at MIT. “However, it doesn’t free up all of it. There’s some piece of your cortex that are still devoted to that control.”

The new study offers hope for those trying to kick bad habits, says Graybiel, senior author of the new study, which appears this week in the Proceedings of the National Academy of Sciences. It shows that though habits may be deeply ingrained, the brain’s planning centers can shut them off. It also raises the possibility of intervening in that brain region to treat people who suffer from disorders involving overly habitual behavior, such as obsessive-compulsive disorder.

Lead author of the paper is Kyle Smith, a McGovern Institute research scientist. Other authors are recent MIT graduate Arti Virkud and Karl Deisseroth, a professor of psychiatry and behavioral sciences at Stanford University.

Old habits die hard

Habits often become so ingrained that we keep doing them even though we’re no longer benefiting from them. The MIT team experimentally simulated this situation with rats trained to run a T-shaped maze. As the rats approached the decision point, they heard a tone indicating whether they should turn left or right. When they chose correctly, they received a reward – chocolate milk (for turning left) or sugar water (for turning right).

To show that the behavior was habitual, the researchers eventually stopped giving the trained rats any rewards, and found that they continued running the maze correctly. The researchers then went a step further, offering the rats chocolate milk in their cages but mixing it with lithium chloride, which causes light nausea. The rats still continued to run left when cued to do so, although they stopped drinking the chocolate milk.

Once they had shown that the habit was fully ingrained, the researchers wanted to see if they could break it by interfering with a part of the prefrontal cortex known as the infralimbic (IL) cortex. Although the neural pathways that encode habitual behavior appear to be located in deep brain structures known as the basal ganglia, it has been shown that the IL cortex is also necessary for such behaviors to develop.

Using optogenetics, a technique that allows researchers to inhibit specific cells with light, the researchers turned off IL cortex activity for several seconds as the rats approached the point in the maze where they had to decide which way to turn.

Almost instantly, the rats dropped the habit of running to the left (the side with the now-distasteful reward). This suggests that turning off the IL cortex switches the rats’ brains from an “automatic, reflexive mode to a mode that’s more cognitive or engaged in the goal of processing what exactly it is that they’re running for,” Smith says.

Once broken of the habit of running left, the rats soon formed a new habit, running to the right side every time, even when cued to run left. The researchers showed that they could break this new habit by once again inhibiting the IL cortex with light. To their surprise, they found that these rats immediately regained their original habit of running left when cued to do so.

“This habit was never really forgotten,” Smith says. “It’s lurking there somewhere, and we’ve unmasked it by turning off the new one that had been overwritten.”

Online control

The findings suggest that the IL cortex is responsible for determining, moment-by-moment, which habitual behaviors will be expressed. “To us, what’s really stunning is that habit representation still must be totally intact and retrievable in an instant, and there’s an online monitoring system controlling that,” Graybiel says.

The study also raises interesting ideas concerning how automatic habitual behaviors really are, says Jane Taylor, a professor of psychiatry and psychology at Yale University. “We’ve always thought of habits as being inflexible, but this suggests you can have flexible habits, in some sense,” says Taylor, who was not part of the research team.

It also appears that the IL cortex favors new habits over old ones, consistent with previous studies showing that when habits are broken they are not forgotten, but replaced with new ones.

Although it would be too invasive to use optogenetic interventions to break habits in humans, Graybiel says it is possible the technology will evolve to the point where it might be a feasible option for treating disorders involving overly repetitive or addictive behavior.

In follow-up studies, the researchers are trying to pinpoint exactly when during a maze run the IL cortex selects the appropriate habit. They are also planning to specifically inhibit different cell types within the IL cortex, to see which ones are most involved in habit control.

The research was funded by the National Institutes of Health, the Stanley H. and Sheila G. Sydney Fund, R. Pourian and Julia Madadi, the Defense Advanced Research Projects Agency, and the Gatsby Foundation.

AF Harvey Prize Lecture

The prize recognizes outstanding contributions to research in the field of medical engineering. Boyden was awarded the prize for his pioneering research contributions to the field of optogenetics, in which neurons are genetically modified to respond to light. He presented his prize lecture at the McGovern Institute on October 22, 2012.

Calcium reveals connections between neurons

A team led by MIT neuroscientists has developed a way to monitor how brain cells coordinate with each other to control specific behaviors, such as initiating movement or detecting an odor.

The researchers’ new imaging technique, based on the detection of calcium ions in neurons, could help them map the brain circuits that perform such functions. It could also provide new insights into the origins of autism, obsessive-compulsive disorder and other psychiatric diseases, says Guoping Feng, senior author of a paper appearing in the Oct. 18 issue of the journal Neuron.

“To understand psychiatric disorders we need to study animal models, and to find out what’s happening in the brain when the animal is behaving abnormally,” says Feng, the James W. and Patricia Poitras Professor of Neuroscience and a member of the McGovern Institute for Brain Research at MIT. “This is a very powerful tool that will really help us understand animal models of these diseases and study how the brain functions normally and in a diseased state.”

The lead author of the Neuron paper is McGovern Institute postdoc Qian Chen.

Performing any kind of brain function requires many neurons in different parts of the brain to communicate with each other. They achieve this communication by sending electrical signals, triggering an influx of calcium ions into active cells. Using dyes that bind to calcium, researchers have imaged neural activity in neurons. However, the brain contains thousands of cell types, each with distinct functions, and the dye is taken up nonselectively by all cells, making it impossible to pinpoint calcium in specific cell types with this approach.

To overcome this, the MIT-led team created a calcium-imaging system that can be targeted to specific cell types, using a type of green fluorescent protein (GFP). Junichi Nakai of Saitama University in Japan first developed a GFP that is activated when it binds to calcium, and one of the Neuron paper authors, Loren Looger of the Howard Hughes Medical Institute, modified the protein so its signal is strong enough to use in living animals.

The MIT researchers then genetically engineered mice to express this protein in a type of neuron known as pyramidal cells, by pairing the gene with a regulatory DNA sequence that is only active in those cells. Using two-photon microscopy to image the cells at high speed and high resolution, the researchers can identify pyramidal cells that are active when the brain is performing a specific task or responding to a certain stimulus.

In this study, the team was able to pinpoint cells in the somatosensory cortex that are activated when a mouse’s whiskers are touched, and olfactory cells that respond to certain aromas.

This system could be used to study brain activity during many types of behavior, including long-term phenomena such as learning, says Matt Wachowiak, an associate professor of physiology at the University of Utah. “These mouse lines should be really useful to many different research groups who want to measure activity in different parts of the brain,” says Wachowiak, who was not involved in this research.

The researchers are now developing mice that express the calcium-sensitive proteins and also exhibit symptoms of autistic behavior and obsessive-compulsive disorder. Using these mice, the researchers plan to look for neuron firing patterns that differ from those of normal mice. This could help identify exactly what goes wrong at the cellular level, offering mechanistic insights into those diseases.

“Right now, we only know that defects in neuron-neuron communications play a key role in psychiatric disorders. We do not know the exact nature of the defects and the specific cell types involved,” Feng says. “If we knew what cell types are abnormal, we could find ways to correct abnormal firing patterns.”

The researchers also plan to combine their imaging technology with optogenetics, which enables them to use light to turn specific classes of neurons on or off. By activating specific cells and then observing the response in target cells, they will be able to precisely map brain circuits.

The research was funded by the Poitras Center for Affective Disorders Research, the National Institutes of Health and the McNair Foundation