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Change Your Mind: Memory and Disease

Thomas Insel Li-Huei Tsai Kerry Ressler Ira Flatow: December 1, 2005; Running Time: 1:25:36

About the Lecture

About the Lecture

How do we distinguish our friends from foes? How does dementia destroy memory? And how can past experience invade the present with destructive force? Scientists are closing in on the biochemical roots of these neurological puzzles.

Thomas Insel describes the profound impact of a small group of neuropeptides on social behavior in animals, from worms to humans. Oxytocin, the hormone which turns on maternal behavior and cognition, turns out to play a large role in determining social memories. Mice whose genes for producing oxytocin are knocked out can’t seem to remember animals they’ve met 30 minutes earlier – what Insel describes as “dense social amnesia.” An area of the brain’s amygdala is particularly rich in oxytocin receptors, and when the peptide is injected into a nearby ventricle, the animals’ social interactions revert more closely to normal behavior. Oxytocin is a useful tool for interrogating the circuitry that enables humans to determine “who’s important to me, who I’d die for, who I’m pair-bonded with, who will take care of me,” says Insel.

Alzheimer’s Disease (AD), which afflicts 20 million people worldwide, begins by literally clogging and tangling the hippocampus, the part of the brain essential for learning and memory. Li-Huei Tsai and other researchers have found “compelling evidence” that a small protein may be critically important in activating AD’s awful atrophy of memory. By manipulating specific enzymes, Tsai has managed to model in animals “all the pathological hallmarks of Alzheimer’s Disease,” and zero in on the source of the plaques and tangles seen in human Alzheimer’s patients. Tsai foresees drug interventions that inhibit these enzymes. But, she says, a big task remains “even after we’re successful in halting a deleterious process--how can we restore learning and retrieve lost memory in AD patients?”

Why is it that only some people exposed to a shocking event develop post-traumatic stress disorder (PTSD)? Kerry Ressler’s research posits that some kind of learning must take place in the brain’s amygdala -- its fear response center—that cannot readily be extinguished. Researchers have tracked down a molecular factor that increases “after learning of fear or extinction of fear.” He believes that if this molecule is somehow blocked from doing its job, then someone suffering from PTSD cannot extinguish fear. In a fortuitous medical convergence, the drug D-cycloserine, which has been approved for years to treat tuberculosis, proves very effective in enhancing the effects of the molecule, and reducing fear of all kinds. One example: When people with fear of heights were given D-cycloserine as they took rides in elevators, they reported a significant, long-lasting reduction in their phobias.

Lecture Details

Location: Picower Institute

About the Speakers

Thomas Insel

Director, National Institute of Mental Health

Thomas Insel received his B.A. and M.D. degrees from Boston University (combined BA-MD program), completed a psychiatric residency at the University of California, San Francisco, and received research training as a clinical fellow in the NIMH intramural program. He spent 15 years at NIMH before leaving for Emory University where he served as Director of the Yerkes Regional Primate Research Center (1994-1999) and the founding Director of the Center for Behavioral Neuroscience (1999-2002) prior to his return to NIMH.

As Director of NIMH, he manages a $1.4 billion budget supporting over 3,000 extramural research project grants in addition to the intramural program.

Li-Huei Tsai

Picower Professor of Neurocience, Department of Brain and Cognitive Sciences, MIT Investigator, Howard Hughes Medical Institute
Professor of Pathology, Harvard Medical School

Li-Huei Tsai initially embarked on a veterinary career in her native Taiwan in 1983, after receiving the D.V.M. degree from National Chung Hsing University. She soon moved to the U.S. to earn an M.S. at the University of Wisconsin, followed by a Ph.D. from the University of Texas Southwestern Medical Center at Dallas. She then joined Cold Spring Harbor Laboratory and Massachusetts General Hospital for postdoctoral training in the area of cancer research and cell cycle regulation. She was appointed Assistant Professor of Pathology at Harvard Medical School in 1994, where she refocused her research on brain development. She was elected investigator of Howard Hughes Medical Institute in 1997, and promoted to Professor of Pathology in 2002.

A major research interest of the Tsai lab is the mechanism leading to neurodegenerative diseases associated with cognitive decline and dementia such as Alzheimer’s Disease. Recently, the Tsai lab has also made contributions to understanding the pathophysiology of neuropsychiatric disorders such as depression.

Tsai has won the Rita Allen Foundation Scholarship, Klingenstein Fellowship for Neurosciences, and Promising Investigator Award from Metropolitan Life Foundation.

Kerry Ressler

Assistant Professor, Department of Psychiatry and Behavioral Sciences, Center for Behavioral Neuroscience, Emory University School of Medicine

Kerry Ressler earned a bachelor’s degree focusing on molecular biology at MIT in 1990, and received an M.D. and Ph.D. from Harvard Medical School in 1997. In 1992 at Harvard, he was the first student of Dr. Linda Buck, helping to identify the molecular organization of the odorant receptor family in mice, for which she shared the Nobel Prize with Richard Axel in 2004.

Ressler's laboratory examines the molecular biology and neural circuitry underlying the learning and unlearning of fear in a variety of behavioral and genetic approaches.

Ira Flatow

Host/Executive Producer, Talk of the Nation: Science Friday

Ira Flatow is also founder and president of TalkingScience, a company dedicated to creating radio, TV and Internet projects that make science “user friendly.” His most recent book is entitled They All Laughed ... From Light Bulbs to Lasers: The Fascinating Stories Behind the Great Inventions That Have Changed Our Lives (HarperCollins, New York).

Flatow's recent honors include: the National Science Board Public Service Award (2005), World Economic Forum Media Fellowship, AAAS Journalism award (2000), the Carl Sagan Award (1999).

About the Host

About the Host

Picower Institute for Learning and Memory

The Picower Institute for Learning and Memory at MIT focuses the talents of a diverse array of brain scientists on a single mission: unraveling the mechanisms that drive the quintessentially human capacity to remember and to learn, as well as related functions like perception, attention and consciousness.