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mcgovern institute for brain research at mit

Issue no. 18 Fall 2010

From the director

This year represents a double anniversary for us – National Medal of Science, and in 2006 Emilio Bizzi was elected president of the American Academy it has been ten years since the founding of the of Arts and Sciences. In addition to their own McGovern Institute and five years since we moved accomplishments, the founding faculty has guided the growth of the institute, including the recruitment of into our new building – so it is a fitting time to cele - 11 new full and associate members since its foundation. brate our past accomplishments and future aspirations. On October 14, we held our 10th anniversary celebration with keynote talks from Gerald Fischbach, Jane Pauley When I became director of the McGovern Institute and Alan Alda. This event was also an opportunity for in 2004, I was privileged to join a truly stellar group me to acknowledge the generosity of our many donors , Jane Pauley, of founding faculty members that had been assembled and to highlight some of our own research accom - Pat McGovern, Lore Harp McGovern, by my predecessor Phil Sharp, the founding director plishments, especially those of our newest colleagues. Alan Alda and of the institute. I am deeply gratified that all of them As we enter our second decade, I am confident that Bob Desimone at the are still here at the institute continuing to contribute these outstanding colleagues will keep the McGovern institute’s anniversary major advances to the field. They have been recognized Institute at the forefront of what I believe will be a celebration. with many honors over the past decade. To mention new age of discovery about the human brain. Photo courtesy of only a few of the highlights, Bob Horvitz shared the Justin Knight 2002 Nobel prize, Ann Graybiel was awarded the 2001 Bob Desimone, Director Institute director Bob Desimone speaking at the 10th anniversary event. understanding the circuits Photo courtesy of Justin Knight of the brain

Research at the McGovern Institute spans many different In his keynote speech, Desimone illustrated his point by presenting some recent dis - questions and technologies. But one overarching theme, coveries, in particular from the new faculty members who have joined the institute according to institute director Bob Desimone, is the need since it was founded in 2000. The following examples are drawn from his talk. to understand the brain in terms of neural circuits. Learning to sing Michale Fee, who joined the McGovern Institute in 2003, studies bird song, an ideal model system for understanding how At the McGovern Institute’s 10th anniversary neural circuits control a complex learned celebration on October 14th, director behavior. Fee, who trained as an engineer, Bob Desimone talked about the institute’s has developed many new technologies to accomplishments over the past decade and make precise recordings from the brains about his aspirations for the future. In par - of birds as they learn to sing. With the ticular he emphasized the importance of help of these tools he has identified a understanding neural circuits. brain region that drives babbling in young birds and he has shown where in the “ have traditionally studied brain trial-and-error learning occurs. He the brain using many different approaches: has also shown profound parallels between genetics, electrophysiology, pharmacology , these circuits and the corresponding human neuroimaging and so on,” he explains . human structures that are disrupted in “But we are now seeing a convergence of Parkinson’s disease. One of his most these approaches at the level of circuits. remarkable findings is the discovery of a We can now start to see beyond the brain’s brain area that controls the song’s tempo: enormous complexity, and to realize that warming this area causes song to speed it is built from circuits that share many up, and cooling it slows the song down. underlying common principles. By under - In work published in October he showed standing how these circuits work, we will how this brain area keeps track of time, gain new depth of insight into the biologi cal through a mechanism that resembles a basis of our own mental lives, while at cascade of falling dominos. It seems very the same time laying the foundations for likely that similar circuits exist in other a new understanding of brain disease.” species including humans, and Fee’s work has pointed the way to finding these “neuronal timers” elsewhere.

2 mcgovern.mit.edu John Gabrieli has found altered patterns of connectivity in patients with schizophrenia or bipolar disorder, including similarities that suggest shared biological mechanisms.

Controlling brain circuits with light that show repetitive grooming behavior The decade of the neural circuit In order to probe, and eventually control, reminiscent of human obsessive-compulsive Desimone cited these examples to illus - the behavior of neural circuits, researchers disorder (OCD). In collaboration with trate his central point: to understand the need new and more precise technologies clinical geneticists he has found that similar brain, we must study its circuits, using a to manipulate the activity of specific genetic variants are associated with human wide range of experimental systems and cells within the living brain. The technique OCD. Most recently, he has developed tech nologies. As the McGovern Institute known as optogenetics, pioneered by an other strain of mice that show both enters its second decade, Desimone is McGovern Institute associate member repetitive behaviors and deficits in social optimistic. “Over the next ten years, with Ed Boyden, has made it possible to achieve interaction, two defining characteristics the help of these new technologies and this using light. Starting with light-sensitive of . Feng is now working to identify others yet to be invented, I believe we will microorganisms, Boyden and colleagues the specific circuits affected in these mutant lay the foundations for a new understanding (including Feng Zhang, who will join the mice. The answers will reveal important of brain function. This in turn will lead to institute in 2011) have been able to isolate clues to human disease, and will provide a a new generation of treatments for brain the light-detecting molecules from these platform for testing new therapies. disorders, beyond anything that we can organisms and express them in the living currently imagine.” brain. This allows researchers to control Brain markers of human disease brain activity with extraordinary precision, Research at the McGovern Institute spans targeting specific cell types and switching many species, but ultimately the brain of them on and off at will. greatest interest is our own. John Gabrieli, who directs the Martinos Imaging Center Optogenetics is now used by hundreds of within the McGovern Institute, is collabo - research labs, including many at MIT, and rating with clinical psychiatrists to study it is also being explored as a new form of schizophrenia and bipolar disorder, and therapy. One early application is likely to be to understand how the genetic risk factors retinal blindness; Boyden and his collabo - for these diseases affect human brain rators have already shown in mice that function. One of his current goals is to optogenetics can restore light sensitivity to examine how these conditions affect the the surviving circuitry of the retina after the so-called default network, an interconnected natural light-sensitive cells have been lost. set of brain structures that are especially active during self-reflection. Modeling disease in mice Many psychiatric disorders have a strong Identifying patterns of brain activity that genetic component, and one important are associated with disease is valuable goal for the McGovern Institute is to because it will help us understand what understand how these genetic alterations brain circuits are affected by different lead to brain dysfunction. Guoping Feng, diseases, leading to new and more biologi - who joined the institute from Duke cally based disease classifications. It can University earlier this year, is using the also help predict who is at risk for these tools of mouse genetics to trace the link diseases and who will respond best to a from genes to pathological behaviors. For given therapy. And finally, understanding example, he has developed strains of mice these patterns of brain activity can help us measure whether a therapy is actually working, perhaps before any behavioral effects are apparent.

3 tenth anniversary celebration

In addition to the presentation by “I want to be helpful in getting Bob Desimone, the anniversary celebration featured keynote talks scientists to communicate their from Gerald Fischbach, Jane Pauley science with more vividness and Alan Alda. Videos of their talks can be seen on our website. and more clarity. ” – Alan Alda

The future of autism research affected and to understand how this causes her situation in public forums, including As scientific director of the Simons deficits in social cognition, he emphasizes her first public acknowledgement of her Foundation , Gerald Fischbach is a leader that we must also study humans, illness at the McGovern Institute opening in in the search to understand the biological “the prime species for autism research 2005. Today Pauley sees a shift in how people causes of autism. in the coming decade.” regard mental illness. Her personal goal, she concluded, is to “banish ugly, out-of-date Autism has a strong genetic component, Normalizing mental illness attitudes” and replace them with “new and identifying the risk genes is a central Leadership Board member and broadcast neural connections, positive associations.” goal for the field. Several of these genes are journalist Jane Pauley spoke candidly about known to be involved in synaptic function, being diagnosed with bipolar depression at The art of science communication pointing to a possible synaptic deficit in the age of 50 and about the need to “nor - When he is not on stage or in a film, autism. Three of these synaptic genes were malize” mental illness. Just as cancer has Alan Alda has worked to advance the public originally identified through a project to moved from the shadows to pink ribbons and understanding of science. Drawing on his understand the effects of black widow spide r races for the cure, she noted, mental illness own experiences as the long-time host of venom. Fischbach cites this as a prime must shed its public aura of fear and shame. the PBS series Scientific American Frontiers , example of curiosity-driven research leading Alda encourages scientists to use their own to unforeseeable practical implications, It was a long struggle to crawl back from voices when communicating their research underlining the importance of pursuing “the dark precipice of mental illness,” to the general public. By posing a series basic and translational goals in parallel. which included a period of hospitalization . of unscripted questions to scientists aroun d In spite of such anguish and anxiety, the world, Alda discovered that “an amazing To understand the actions of these genes, Pauley says she had hope even from the thing happened on their end: the real ‘them’ mouse models are essential, says Fischbach . beginning. Medicine helped, but Pauley came out. They weren’t lecturing me, but But to identify the specific circuits that are also credits the capacity to open up about connecting with me and trying to get me to understand. These conversation modes brought out not only their own personalities, but the science through their personalities.”

Alda speculates that this kind of commu - nication must somehow involve the brain’s social communication systems. He challenged researchers to unravel the neurological basis for the kind of communication “that makes us human, and that someday may help scientists all over the world to speak in their own voices.”

Gerald Fischbach (left), Jane Pauley, and Alan Alda. Photos courtesy of Justin Knight

4 mcgovern.mit.edu new funding for new knowledge

New Gifts Support China Collaborations and Disease Research

We are delighted to report on three new We have also received an anonymous gift contributions to the McGovern Institute of $150,000 in support of Ann Graybiel’s this fall. Parkinson’s disease research. This contri - bution follows on a similar $100,000 Hugo Shong, General Partner of IDG anonymous gift to the Graybiel lab last year. Capital Partners, has made a $1 million “This gift is extraordinary for us,” Graybiel pledge to support new collaborations says. “It allows us to push to the very edge between the McGovern Institute and China. of what is technically possible in our lab. It will help us to advance our understand - “This pledge is my gift to Pat McGovern ing of the and, ultimately, in honor of the tenth anniversary of the to improve therapies to treat or prevent Hugo Shong, General Partner of IDG Capital McGovern Institute,” said Shong, who neuropsychiatric conditions like Parkinson’s Partners, pledges support for new collaborations joined IDG in 1991. The contribution, disease. I am profoundly inspired by between the McGovern Institute and China. which builds upon a gift by Shong to the this gift and will transmit my inspiration institute in 2008, is to be used for the as much as I can to the young people development of McGovern programs in working in my lab.” China over the next ten years. Robert Buxton, a member of the McGovern In renewing his financial commitment, “Global collaborations are critical to the Institute Leadership Board and Executive Buxton cites the significance of the inter - advancement of our understanding of Vice President of Peter Kimmelman Asset disciplinary approach at the McGovern the brain,” says institute director Bob Management LLC, has once again chosen Institute. Such an approach, he feels, Desimone. “We are enormously grateful to support disease-based research at the gives McGovern an edge over other for Hugo’s gift, which will allow us to institute. For Buxton, whose son suffers institutions. “There is a clear mission at keep up our end of the new Chinese from serious mental illness, the motivation the McGovern Institute,” he says. “They collaborations that his original contribu - for his gift is crystal-clear. “Autism and have top-notch scientists using a systems tion helped us to establish.” bipolar disorder have been devastating for engineering approach to understand the our family,” Buxton explains. “Research brain. It will be these pathfinders who at the McGovern Institute will be the eventually find the answers to the devastat - salvation for kids and adults affected ing disorders of the brain.” by these disorders.”

Leadership Board member Robert Buxton talks with Ann Graybiel. Photo courtesy of Justin Knight

5 institute news

Fellowships Awarded to Four Young Neuroscientists

Four graduate students at the McGovern Institute are the newly announced recipients of fellowships that are made possible through the generosity of our donors. The students presented their research to the Leadership Board and Friends of the McGovern Institute at a private event preceding the 10th anniversary celebration in October.

Mark Howe, a graduate student in Ann Graybiel’s lab, is the first recipient Newly appointed fellows Mark Howe (top left); of the Gorenberg Fellowship, which was Vivian Hsieh (top center); Zeynep Saygin newly established by Leadership Board (top right); and Retsina Meyer (left, speaking member Mark Gorenberg. Howe studies with Leadership Board member Pat Poitras) dopamine activity in the basal ganglia, Photos courtesy of Justin Knight deep brain structures that are involved in both directing and motivating behavior. By studying the mechanisms in basal ganglia circuits that allow animals to learn and execute a new set of behaviors, he hopes to pinpoint elements of the circuit that are affected in disorders like Parkinson’s disease and drug addiction. The Sheldon and Janet Razin Fellowship Retsina Meyer was awarded the Shoemaker was awarded to Zeynep Saygin, a graduate Fellowship for her research in Ki Goosens’ Vivian Hsieh received the graduate student in John Gabrieli’s lab, for her lab. Meyer is studying how stress contributes student fellowship of the Friends of the research on the development of new methods to the formation of fearful memories. McGovern Institute for her work in for visualizing long-distance connections By understanding these mechanisms, it Alan Jasanoff’s lab. Hsieh is developing in the human brain. Saygin is using a method may be possible to develop more effective new molecular sensors that she hopes called diffusion tensor imaging, or DTI, treatments for anxiety disorders, depression , will expand our ability to image the living to examine the connections to and from and other psychiatric disorders. brain in all its biochemical complexity. brain regions that are implicated in fear, anxiety, and potentially in conditions such as depression, anxiety disorders and autism.

Institute Researchers Make Strong Showing at San Diego Meeting

The McGovern Institute was strongly institute presented 76 posters and talks represented at the Society for at the November meeting, almost twice annual meeting in San as many as last year. Diego, California. Members of the

6 mcgovern.mit.edu research news

formation appears to be an innate tendenc y that is fine-tuned by experience — specifi - cally, by the costs and rewards of certain choices. Her study is published in the Oct 25 issue of the Proceedings of the National Academy of Sciences , with an accompanying The song of the zebra finch lasts about one second, commentary by Terrence Sejnowski of the and is almost identical from one performance to Salk Institute. The story was also picked the next. up by WBUR, Boston’s NPR station. Image courtesy of Dan Rubin and Michale Fee In a paper published in the journal Nature Communications , Tomaso Poggio As anyone who as ever picked up a guitar describes a new computer system that or a tennis racket knows, precise timing can classify mouse behaviors from video is often an essential part of performing recordings. The new system is as accurate complex tasks. By studying the brain circuits as human observers, and will be a valuable that control bird song, Michale Fee has tool for measuring the behavioral effects identified a “chain reaction” of brain activity of drugs and gene that target that appears to control the timing of the the . song. His findings are published in the Oct 24 issue of Nature . Understanding how the brain recognizes objects is a central challenge for under - Most people have habits that guide them standing biological vision, and for designing through daily life. The brain patterns that artificial vision systems. In a study published drive these habitual behaviors are not in the Sept 23 issue of the journal , well-understood, but a new study out of Jim DiCarlo provides new evidence that Tomaso Poggio has developed a computer method Ann Graybiel ’s lab shows that habit the brain learns to solve the problem of that can automatically classify mouse behaviors. object recognition through its vast experience in the natural world.

awards and honors

With an h-index value of 92, Tomaso Poggio The Paul G. Allen Family Foundation is now considered among the most has named Ed Boyden among the first highly cited Italian scientists, according scientists to receive their Distinguished to the Virtual Italian Academy (VIA). Investigator Award. The seven inaugural The h-index, which is used to measure investigators were selected based on a scientist’s productivity and apparent their “potential for major breakthroughs” scientific impact, is based on how many and for research that complements highly cited papers a scientist has pub - work being done at the Allen Institute lished, and how many times each of for Brain Science. Boyden’s $1.3 million Ed Boyden develops tools to control the activity of these papers is cited in other publications. award will fund his efforts to invent individual in the brain. Poggio’s publication profile extends beyon d new electronics and software for creating computational neuroscience into other real-time electrical maps of the brain disciplines, earning him the VIA title of in three dimensions. “most eclectic scientist.”

7 events

McGovern Institute 10th Anniversary Photo Gallery

On October 14, Pat and Lore McGovern were joined by over 200 friends and supporters of the McGovern Institute to celebrate the 10th anniversary of the institute’s founding. More photos from the event, along with videos of the keynote talks, can be found on our website.

The entire photo album from this event can also be viewed on our facebook page: http://www.facebook.com/mcgoverninstitute Guests at the 10th anniversary celebration mingle during a cocktail reception (left); Pat and Lore McGovern give dinner remarks (top right); Guests watch a soundsuit presentation choreographed by Nick Cave of the Art Institute of Chicago (bottom right). Photos courtesy of Justin Knight

Brain scan Editors: Charles Jennings, Julie Pryor The McGovern Institute for Brain Research at MIT is led by a team of Quarterly Writer: Cathryn M. Delude world-renowned neuroscientists committed to meeting two great challenges Newsletter of Development Officer: Laurie Ledeen of modern science: understanding how the brain works and discovering the McGovern Design: Sametz Blackstone Associates, Boston new ways to prevent or treat brain disorders. The McGovern Institute was Institute established in 2000 by Patrick J. McGovern and Lore Harp McGovern, who are committed to improving human welfare, communication and understanding through their support for neuroscience research. The director is Robert Desimone, formerly the head of intramural research at the National Institute of Mental Health.

Further information is available at: http://mcgovern.mit.edu © Copyright 2010, McGovern Institute for Brain Research at MIT

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