Altering a protein makes mice less fearful

A University of Iowa study shows that loss or chemical inhibition of a protein, known as acid sensing ion channel protein (ASIC1a), reduces innate fear behavior in lab animals, making normally timid mice relatively fearless. The findings might provide useful insight into anxiety disorders and may even point the way to a new therapeutic target.

For humans and other animals, some fears seem to be, in large part, instinctive and inborn rather than learned. For example, laboratory animals fear certain predators even though they have never been exposed to a predator. However, little is known about the brain mechanisms involved in innate fear responses.

The UI study, published in the scientific journal, Biological Psychiatry, and available online July 30, shows that disrupting the ASIC1a protein alters innate fear reactions in mice and suggests that this protein may be a critical component of the brain systems that underlie innate fear.

The UI team, led by John Wemmie, M.D., Ph.D., assistant professor of psychiatry in the Roy J. and Lucille A. Carver College of Medicine, focused on ASIC1a because earlier research from the lab had shown that the protein was important in learned fear.

The new study examined the protein's role in innate fear by disrupting ASIC1a in mice and observing the effect on several well-studied innate fear behaviors.

Mice that lack the protein were significantly less fearful of open spaces, loud noises and predator odor than normal mice.

In the odor test, the researchers placed a beaker containing a fox-odor chemical in the mouse enclosure. Normal mice froze when they smelled the chemical and avoided the beaker. In contrast, mice lacking the ASIC1a protein showed a much-reduced freezing response and even climbed onto the beaker. The team showed that the loss of ASIC1a did not affect the mouse's sense of smell.

"These lab animals have never been exposed to a predator. The freezing

Contact: Jennifer Brown
University of Iowa

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