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Study identifies gene in mice that may control risk-taking behavior in humans

Long-term behavioral studies of mice with no neuroD2 genes were not possible because these mice die within a few weeks of birth.

In one experiment, mice were exposed to an adverse stimulus coupled with a non-adverse stimulus, a tone followed by a mild foot shock. Normal mice crouch down and stop moving the next time they hear the tone, a physiologic response that indicates they expected a shock. The mice remembered the experience. However, those with a single copy of the neuroD2 gene did not respond to the tone like the normal mice did, researchers found. These mice did not freeze their movements as often in anticipation of the mild shock.

To assess the level of unconditioned fear in mice with a single copy of the neuroD2 gene, researchers put them into a situation that would elicit a fear response in normal mice. They used a maze elevated 40 centimeters above a tabletop where mice had the option to walk along narrow, unprotected walkways or arms with protective walls. Half of the time the neuroD2-deficient mice chose the unprotected arms, whereas the normal mice almost always chose the protected arms, Olson said.

"All of this matches very well with previous observations that the amygdala is responsible for fear, anxiety and aggression," said Olson. "Now we're seeing that the neuroD2-deficient mice, when compared to normal littermates, show a profound difference in unconditioned anxiety levels as well as their ability to form emotional memories."

Olson noted that the dosage of neuroD2, one copy versus the normal two copies, was important for how much fear, anxiety and aggression the mice displayed.

"These findings are new to science," said Olson, who is also an associate professor in pediatrics at the University of Washington School of Medicine. "The contribution we have made is showing that neuroD2 is related to the development of the amygdala. This is the first time that a specific neurodevelopmental gene has been related to these
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Contact: Dean Forbes
dforbes@fhcrc.org
206-667-2896
Fred Hutchinson Cancer Research Center
26-Sep-2005


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