University of Texas Medical Branch at Galveston
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DATE SENT: Dec. 8, 1997
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until 2 p.m. Eastern Time, Wednesday, Dec. 10, 1997
TO CONTACT SOURCES:
Contact Patricia Shinnick-Gallagher at (409) 772-9648 or
Robert Malenka at (808) 885-5969 (on or before Dec. 13) or (415) 476-7590 (after Dec. 14).
To obtain Nature articles and commentaries, call FaxBack at (800) 570-7747.
SCIENTISTS SHOW HOW WE LEARN TO BE SCARED OF HARMLESS THINGS
GALVESTON, Texas -- Why would a grown man walking down a dark alley be daunted by the sound of rustling leaves or a creaky gate, though the alley is deserted? How might a smart, well-prepared lawyer be reduced to trembles at the thought of presenting her case in a crowded but controlled courtroom?
These unfounded apprehensions -- and more serious ones such as phobias and anxiety disorders -- are all caused by one emotion: fear. New research, appearing as two papers in the Dec. 11 Nature, suggests how we may become frightened of things that can't hurt us. It also points to ways we might one day overcome powerful emotional associations, including those resulting from child abuse, war and other trauma.
The new results also offer the most compelling support yet for a long-held theory of how we learn. Called long-term potentiation, or LTP, this theory states that new information is cemented into memory when nerve cells in the brain strengthen communication between themselves. Nerve cells talk to each other by releasing chemicals that travel across the gaps, or synapses, that separate them. Usually, the chemicals attach to the next nerve in the communication chain, causing it to fire and release its own synaptic messengers, which excite the next nerve, and so on. Learning is thought to happen when a recurring stimulus -- such as repeating an unfamiliar phone number -- makes the cells positioned later in the chain respond more strongly. The strengthened response appears in the downstream cells as increased electrical activity, called potentiation.
Researchers have created models of this potentiation by studying pieces of brain in plastic laboratory dishes. However, critics often have argued that such an exercise is meaningless because it doesn't show that real animals actually learn that way.
To clear up that controversy, scientists at New York University and the University of Texas Medical Branch at Galveston (UTMB) measured the strength of synaptic connections in rats that had learned to fear a harmless tone. Joseph LeDoux and colleagues in New York (authors of the first paper) and Margaret McKernan and Patricia Shinnick-Gallagher in Galveston (authors of the second) paired the sound with a mild electric shock. Then, they measured electrical activity in the rats' amygdala, a part of the brain thought to play a role in fearful emotions.
Both research groups showed that, when presented with the harmless tone alone, the amygdala nerve cells of rats that had come to expect a shock with the tone were more sensitive to the sound than the amygdala nerve cells of rats that hadn't learned the association.
"This research is a direct confirmation that synaptic communication has been strengthened by behavior," says Robert C. Malenka, a neuroscientist at the University of California at San Francisco who studies LTP using in vitro brain preparations. Malenka co-authored a "News and Views" commentary that accompanies the Nature articles.
Fear is fundamental to most organisms' survival. By learning to avoid certain threats, we protect ourselves. But emotional memories also can be disturbing. So far, scientists haven't found drugs that successfully uncouple the kinds of associations that might throw a rape victim into hysterics at the whiff of a particular cologne, or that quell the jitters of a person with post-traumatic stress disorder.
"The learned fear response is fundamental, and it's very long-lasting," says Shinnick-Gallagher, professor of pharmacology and toxicology at UTMB. "To remove that fear -- to decondition it -- is much more difficult than establishing the association in the first place."
Many anti-phobia and anti-anxiety drugs, Gallagher says, were designed to treat mood disorders such as depression. Some of them cause unwanted side effects, such as amnesia and cognitive impairment, and many require weeks to take effect. Gallagher and others believe that's because these drugs target mechanisms only distantly related to fear itself.
Looking for mechanisms more fundamental to fright, researchers have found numerous hints that a neurotransmitter called glutamate might be responsible for the learned-fear response. But that association had never been verified directly -- until now. Using a sophisticated technique called patch clamping, Gallagher and McKernan showed that fear-conditioned rats release more glutamate from the nerves that transmit auditory signals to the amygdala. If scientists can find a way to block that extra glutamate release, they may be able to help people step up to those scary podiums or face old demons without distress.
"Phobias, post-traumatic stress disorder, anxiety disorders, all of these impair people's ability to function in society--to achieve their full potential," says Gallagher. "Our goal, as pharmacologists, is to find drugs that will decrease learned fear responses that are detrimental while preserving life-saving fear responses and cognition."
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