Br aın SCAN 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 “Neuroscientists 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 autism. 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.