Brain Protein May Play Role in Innate and Learned Fear

Collaborative study conducted with Nobel Prize recipient Eric Kandel

November 17, 2005

Cindy Lepore
Public Affairs

Belmont, MA - A protein expressed in the brain's amygdala region is linked to the ability to produce the fear response, report researchers at Harvard-affiliated McLean Hospital. The finding could lead to new treatments for a variety of mental disorders, including post-traumatic stress disorder and generalized anxiety.

In a paper (PubMed) published in the November issue of Cell, the researchers reported that the protein stathmin is essential for the fear response-both the expression of innate fear and the formation of memory for learned fear.

Previous studies had shown that the amygdala, a brain structure important for emotional responses, is the place where fear memory is formed.

"This is the first time it has been shown that the protein called stathmin-the product of the stathmin gene-is linked to fear conditioning pathways," said Vadim Bolshakov, PhD, director of the Cellular Neurobiology Laboratory at McLean Hospital. The study is the collaborative effort of Bolshakov's lab at McLean and those of Eric Kandel at Columbia University and Gleb Shumyatsky of Rutgers. Kandel is the winner of the 2000 Nobel Prize in physiology or medicine.

The researchers for some time have been studying how changes in the brain may affect learning and memory. In earlier animal studies, Bolshakov and Kandel were able to measure changes in the brain and correlate them with changes in behavior associated with learning.

This study, using mice, demonstrated that those that were genetically modified so they would not produce stathmin showed deficits in neural transmission and exhibited decreased memory in fear conditioning and the failure to recognize danger in innately aversive environments. Learned fear develops after conditioning and lasts for life-no longer needing molecular level," Bolshakov concluded.

"The evidence that stathmin is important in the regulation of fear suggests that stathmin knockout mice can be used as a model of anxiety states or mental disorders with innate and learned fear components," the paper said.

In the future, these animal models may be used to develop new anti-anxiety drugs, Bolshakov added.

"This is also one of the first studies showing the interaction between learned and innate components of fear behavior at the molecular level," Bolshakov said. "These findings provide some new insights into learning and memory mechanisms."

In addition to Bolshakov, McLean's research team also included Ryong-Moon Shin, MD, PhD, Keith Tully, PhD, and Evgeny Tsvetkov, PhD.

McLean Hospital, consistently ranked the nation's top psychiatric hospital by U.S. News & World Report, is an affiliate of Harvard Medical School and Massachusetts General Hospital and a member of Partners HealthCare.

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