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McGovern Institute: Ten Years of Understanding the Brain in Health and Disease

10/14/2010 4:00 PM 46
Robert Desimone, Director, McGovern Institute; The Doris and Don Berkey Professor of Neuroscience

Description: Psychiatric illness and neurological disorders such as autism, depression, and Alzheimer's disease cause countless families to suffer, and require prodigious economic resources to manage. Now, thanks to major advances in genomics, systems neuroscience, and human brain imaging, says Robert Desimone, scientists are unlocking key secrets in how the human brain functions, work that may herald new and more effective therapies for neural disorders.

In his keynote address, Desimone pays tribute to McGovern Institute researchers who are tackling a common problem: understanding the neural circuit. Ed Boyden works with different wavelengths of light to turn targeted cells on and off in living brains, "much the way a conductor controls musicians in an orchestra," says Desimone. Boyden has focused in particular on the "straightforward circuit" of the retina, replacing dead photoreceptors with genetically manipulated, light"sensitive molecules so that mice with impaired vision see light again. Someday, this research could help people with similar kinds of blindness.

McGovern researchers are also untangling the more complex neural circuitry associated with psychiatric diseases and developmental disorders. Michale Fee's model of the neural basis for bird song identified a brain structure that has an exact parallel in mammals -- a loop connecting the cortex and basal ganglia in which motor sequences move through a chain of neurons in precise order, "like dominoes falling." A mistake in this circuit in humans could result in behavioral disorders. Guoping Feng demonstrates that a single malfunctioning synaptic protein can wreak havoc on the basal ganglia, disrupting learning in humans. He has also determined that related circuits bearing gene mutations create behavior in mice that remarkably mirrors obsessive compulsive disorders in humans.

Yingxi Lin has identified a gene that helps the brain regulate the excitatory and inhibitory synapses, keeping neurons in balance, the way a thermostat regulates temperature in a room. Without this gene, mice "get too much excitation" and develop seizure disorders. She has discovered a comparable gene in autistic people, who also are prone to seizures. Other McGovern researchers are developing next generation diagnostic tools. John Gabrieli has mapped out the circuits central to high level cognitive functions, and will soon be deploying a new kind of imaging that gives a precise picture of dynamic changes in brain states, measured in milliseconds. And Alan Jasanoff uses genetic engineering techniques to create new molecules that act as sensors, showing the release and flow of chemicals in the brain that can highlight both healthy and diseased circuitry. Insights from McGovern research, says Desimone, "will lay down the foundation for therapeutics of the future."

About the Speaker(s): Prior to joining the McGovern Institute in 2004, Robert Desimone was director of the Intramural Research Program at the National Institutes of Mental Health, the largest mental health research center in the world. He is a member of the National Academy of Sciences and the American Academy of Arts and Sciences and a recipient of numerous awards, including the Troland Prize of the National Academy of Sciences, and the Golden Brain Award of the Minerva Foundation. Desimone received his B.A. from Macalester College and his Ph.D. from Princeton University.

Host(s): School of Science, McGovern Institute for Brain Research at MIT

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