Ann Graybiel studies the basal ganglia, forebrain structures that are profoundly important for normal brain function but are also implicated in Parkinson’s disease, Huntington’s disease, obsessive-compulsive disorder, and addiction.
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Lunch with a Laureate: H. Robert Horvitz
Video Profile: Tomaso Poggio
Tomaso Poggio develops computational models of brain function in order to understand human intelligence and to build intelligent machines that can mimic human performance. Learn more about Tomaso Poggio here.
2010 Scolnick Prize Lecture: Yuh-Nung and Lily Jan
The McGovern Institute awarded the 2010 Edward M. Scolnick Prize in Neuroscience to Lily and Yuh-Nung Jan of the University of California, San Francisco. In this video, Yuh-Nung Jan delivers the first part of a joint prize lecture entitled, “Dendrite morphogenesis and channel regulation: implications for mental health and neurological disorders.” McGovern Institute director, Bob Desimone, greets the crowd and the Jans lecture is introduced by Nobel laureate, H. Robert Horvitz.
The second half of the lecture is delivered by Yuh-Nung’s wife and colleague, Lily Jan.
Novel MRI sensor provides molecular view of brain
Alan Jasanoff is developing a new generation of brain imaging technologies to study the neural mechanisms of behavior. In this video press release, Jasanoff discusses his latest findings published in Nature Biotechnology on February 28, 2010. In this study, Jasanoff’s team designed a new MRI sensor that responds to the neurotransmitter dopamine, an achievement that may significantly improve the specificity and resolution of future brain imaging procedures.
Video Profile: Alan Jasanoff
Functional magnetic resonance imaging (fMRI) has revolutionized our understanding of the human brain, but the method is now approaching the limit of its capabilities. Alan Jasanoff hopes to break through this limit and to develop new technologies for imaging the molecular and cellular phenomena that underlie brain function.
How we read each other’s minds: Rebecca Saxe at TED2009
Sensing the motives and feelings of others is a natural talent for humans. But how do we do it? Here, Rebecca Saxe shares fascinating lab work that uncovers how the brain thinks about other peoples’ thoughts — and judges their actions.
Doris and Donald Berkey ’43, SM’43
Doris and Donald Berkey ’42, SM ’43, of Naples, Florida, have donated $3 million to endow an MIT Professorship in neuroscience, with Robert Desimone, Director of the McGovern Institute, as the first incumbent.
Our decision to endow this chair reflects our belief that a better understanding of the brain will help to prevent some of the suffering caused by psychiatric disease, the Berkeys say. “We are delighted to learn that Bob Desimone and the McGovern Institute share this goal.”
For Don Berkey, attending MIT was a childhood dream come true. At MIT he studied mechanical engineering at both the undergraduate and masters levels. “My mind was mechanical and I wanted to understand how things work,” he explains. After receiving his SM in 1943, he joined General Electric (GE) to work on jet engines during the second world war. He rose through the managerial ranks, becoming General Manager of the Jet Engines Department and he holds several patents in jet engine design, including the high by-pass turbine engine. GE had won a $465 million military contract to design a more efficient engine for the C5A, a large military transport plane that had long-range requirements. “Our engine was 30% more fuel efficient,” he says, “and it’s the basic design for all the high-bypass jet engines that you see today with their big fans enclosed on the wings.”
For his last seven years at GE, Don headed the Energy Systems and Technical Division as Vice President, working to advance technologies for solar energy, coal, nuclear, and other forms of energy during President Carter’s “war on energy” years. When that focus receded during the Reagan presidency, Berkey retired in 1982 at the age of 62. Don and Doris divided their time between Cape Cod and Florida, and have taken up golfing, boating, and competitive duplicate bridge. They keep abreast of technology developments by reading MIT’s Technology Review and other publications.
“In thinking about how we could focus our philanthropy,” explains Don, “we decided to support research related to mental illness because our family, like so many others, has been touched by these issues. We went to the internet to learn about research in this area, and we were ultimately led to the McGovern Institute. In speaking with Bob Desimone, we were impressed by his experience in mental health research and by his accomplishments at the National Institute of Mental Health. We were also encouraged by the direction he has been leading the McGovern Institute and, in particular, by the focus of the new Poitras Center for Affective Disorders Research.”
Finally, after speaking with MIT’s Provost, Rafael Reif, the Berkeys decided to create the Don and Doris Berkey Professorship naming Desimone as the first incumbent.
“I agreed that Bob Desimone was the perfect choice for this professorship given his long track record of achievements in basic neuroscience research that is beginning to have clinical relevance to psychiatric disorders,” says Reif.
Desimone feels profoundly grateful for the Berkey’s generosity. “This professorship will support my ongoing efforts to nurture a new generation of neuroscientists dedicated to linking basic research to improving the lives of people struggling with psychiatric disorders.”
Researchers find new actions of neurochemicals
Although the tiny roundworm Caenorhabditis elegans has only 302 neurons in its entire nervous system, studies of this simple animal have significantly advanced our understanding of human brain function because it shares many genes and neurochemical signaling molecules with humans. Now MIT researchers have found novel C. elegans neurochemical receptors, the discovery of which could lead to new therapeutic targets for psychiatric disorders if similar receptors are found in humans.
Dopamine and serotonin are members of a class of neurochemicals called biogenic amines, which function in neuronal circuitry throughout the brain. Many drugs used to treat psychiatric disorders, including depression and schizophrenia, target these signaling systems, as do cocaine and other drugs of abuse. Scientists have long known of a class of biogenic-amine receptors that are G protein-coupled receptors (GPCRs) and that, when activated, trigger a slow but long-lasting cascade of intracellular events that modulate nervous system activity.
A study in the July 3 issue of Science has found that in C. elegans these chemicals also act on receptors of a fundamentally different type. These receptors are chloride channels that open and close quickly in response to the binding of a neurochemical messenger. By allowing the passage of negatively charged chloride ions across the cell membrane, chloride channels can rapidly inactivate nerve cells.
“These results underscore the importance of determining whether, as in the C. elegans nervous system, a diversity of biogenic amine-gated chloride channels function in the human brain,” said H. Robert Horvitz of the McGovern Institute for Brain Research at MIT and senior author of the study. “If so, such channels might define novel therapeutic targets for neuropsychiatric disorders, such as depression and schizophrenia.”
In 2000, Horvitz’s group discovered that serotonin activates a chloride channel they called MOD-1, which inhibits neuronal activity in C. elegans.
In the current study, Niels Ringstad and Namiko Abe, a postdoctoral researcher and an undergraduate in Horvitz’s laboratory, respectively, looked for other ion channels that could be receptors for biogenic amines. Using both in vitro and in vivo methods, they surveyed the functions of 26 ion channels similar to MOD-1 and found three additional ion channels with an affinity for biogenic amines: dopamine activates one, serotonin another, and tyramine (the role of which in the human brain is unknown) a third. All three were chloride channels, like MOD-1.
“We now have four members of a family of chloride channels that can act as receptors for biogenic amines in the worm,” Ringstad said. “That these neurochemicals activate both GPCRs and ion channels means that they can have very complex actions in the nervous system, both as slow-acting neuromodulators and as fast-acting inhibitory neurotransmitters.”
It is unknown as yet whether an equivalent to this new class of worm receptor exists in the human brain, but Horvitz points out that worms have proved remarkably informative for providing insights into human biology. In 2002, Horvitz shared the Nobel Prize in Physiology or Medicine for the discovery based on studies of C. elegans of the mechanism of programmed cell death, a central feature of some neurodegenerative diseases and many other disorders in humans.
“Historically, studies of C. elegans have delineated mechanisms of neurotransmission that subsequently proved to be conserved in humans,” says Horvitz, the David H. Koch Professor of Biology at MIT and a Howard Hughes Medical Institute Investigator. “The next step is to look for chloride channels controlled by biogenic amines in mammalian neurons.”
This study was supported by the NIH, the Howard Hughes Medical Institute, the Life Sciences Research Foundation, and The Medical Foundation.
MIT’s McGovern Institute honors Emory neuroscientist for contributions to psychiatry
The McGovern Institute for Brain Research at MIT announced today that Michael Davis, a neuroscientist at Emory University in Atlanta GA, will be the 2008 recipient of the Edward M. Scolnick Prize in Neuroscience. The Scolnick Prize is awarded annually by the McGovern Institute to recognize an individual who has made outstanding advances in the field of neuroscience. Dr. Davis, who is the Robert W. Woodruff Professor of Psychiatry and Behavioral Sciences at Emory University School of Medicine, will receive the 2008 prize for his work on the neural basis of fear and its applications to psychiatric research.
“We are delighted to honor Mike Davis with this award”, said Robert Desimone, director of the McGovern Institute and chair of the selection committee. “Not only has he made many important contributions to basic neuroscience, his work also represents one of the best examples of bench-to-bedside translational research in psychiatry.”
In work that spans three decades, Davis has provided fundamental insights into the neural basis of fear and anxiety. His early research exploited the startle reflex of rats in response to a sudden noise. He showed that this response is sensitive to drugs that reduce anxiety in humans, and in a classic 1982 paper he traced the entire brain pathway that underlies the startle reflex, paving the way for detailed studies of the neural mechanisms that underlie anxiety.
Like Pavlov’s dogs that were conditioned to associate a bell with food, rats and humans can learn fearful associations. The fear conditioning paradigm has been immensely influential in neuroscience, providing for example one of the earliest and best demonstrations of the importance of synaptic changes in learning. Davis has contributed importantly to this field, showing that fear learning is controlled by a class of molecules known as NMDA receptors, acting within a brain structure called the amydgala.
The ‘flip side’ of associative learning is extinction, a process by which learned associations such as fearful memories eventually disappear. Extinction is not merely the gradual decay of memory. Instead, Davis has shown that extinction involves an active process that, like the acquisition of fear memories, depends on NMDA receptors. Understanding the balance between acquisition and extinction of fearful memories is of great importance for psychiatric conditions such as anxiety disorders and PTSD, and based on his studies with rats, Davis proposed that drugs that promote NMDA receptor signaling could be used therapeutically to enhance fear extinction in humans.
In collaboration with clinical colleagues at Emory, Davis recently confirmed this idea, showing that the drug D-cycloserine can enhance the effects of psychotherapy as a treatment for fear of heights. This approach also shows promise for treating other disorders, including obsessive-compulsive disorder, social phobia, panic disorder and post-traumatic stress disorder (PTSD); Davis is currently testing D-cycloserine, in combination with virtual reality-based psychotherapy, on Iraq veterans suffering from PTSD.
The McGovern Institute will award the Scolnick Prize to Dr. Davis on Monday April 14, 2008, at 4pm. Dr. Davis will deliver a lecture entitled “Neurobiology of Fear, Anxiety and Extinction: Implications for Psychotherapy”, followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex, 43 Vassar Street (building 46, room 3002) in Cambridge. The event is free and open to the public.
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About the Edward M. Scolnick Prize in Neuroscience
The Scolnick Prize, awarded annually by the McGovern Institute, is named in honor of Dr. Edward M. Scolnick, who stepped down as President of Merck Research Laboratories in December 2002 after holding Merck’s top research post for 17 years. Dr Scolnick is now an associate member at the Broad Institute of MIT and Harvard, where he directs the Stanley Center for Psychiatric Research. He also serves as a member of the McGovern Institute’s governing board. The prize, which is endowed through a gift from Merck to the McGovern Institute, consists of a $50,000 award, plus an inscribed gift, and is given each year to one recipient.
About the McGovern Institute for Brain Research at MIT
The McGovern Institute for Brain Research at MIT is led by a team of world-renowned, neuroscientists committed to meeting two great challenges of modern science: understanding how the brain works and discovering new ways to prevent or treat brain disorders. The McGovern Institute was 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://web.mit.edu/mcgovern/