Brain Facts

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How Fear Works In the Brain

Scientists hope that by understanding how fear works in the brain they will be better equipped to treat fear-based disorders, such as post-traumatic stress and panic attacks. One of their study targets is a brain chemical involved both in learning to be afraid, as well as in curbing already existing fear.  

In new research, scientists at Emory University recently showed that mice lacking this chemical, known as brain-derived neurotrophic factor, or BDNF, had trouble remembering to fear a trauma inflicted upon them, in this case, electric shocks.    

In humans, the finding ultimately could lead to preventing the emotional and often disabling after-effects of trauma, such as the anxiety, flashbacks and other symptoms suffered by more than 5 million Americans every year.

If you could find a way to block the growth factor at the time of some trauma, we might be able to prevent the emotional consolidation of that memory, said Kerry Ressler, a researcher at Emory University's Yerkes National Primate Research Center, an associate professor of psychiatry and behavioral sciences at Emory University School of Medicine, and a Howard Hughes Medical Institute investigator.  For example, if you were bitten by a dog, we might be able to keep you from later being afraid of dogs.

Such a treatment, a drug perhaps, could be given at the scene of a trauma, in an emergency room, even on the battlefield.  But it would not necessarily have to be administered immediately. Memories aren't made instantly, Ressler said. They take hours or days to consolidate. 

In mice, the function of BDNF depends on which part of the brain is activated, and when. The parts of the brain involved in learning to be afraid are different from the parts of the brain involved in the inhibition and recovery from fear, Ressler said.

Two regions of the prefrontal cortex in the mouse brain secrete the chemical. When released in the prelimbic part of the prefrontal cortex, it solidifies the memory of a trauma. In the infralimbic part of the prefrontal cortex, however, it helps the animal cope with fear and anxiety.

We don't think that the production of BDNF is required for the expression of fear, but the learning of fear, Ressler said.

Working with Ressler, postdoctoral associate Dennis Choi and their colleagues studied a strain of genetically engineered mice lacking the BDNF gene in certain parts of the brain, including the prelimbic cortex. The mice, who were electrically shocked just after hearing a certain tone, gradually learned to fear that tone--and showed their fear by freezing. They ran around and responded to shocks, and demonstrated fear of the tone in the moment.

However, they had trouble holding onto their fear memories as time passed. After learning to fear the tone, the BDNF-altered mice froze less, compared to normal mice, one hour or a day  later. The researchers also tried a different approach: They injected mice with a virus that eliminates the BDNF gene in the prelimbic cortex and saw similar results.

Scientists think it works the same way in humans.  Different parts of the human brain release a similar chemical that has the same functions and the same impact as it does in mice. That's what they are trying to find out.

In related research that raises another potential application, it also might be possible to use BDNF to strengthen cognitive behavioral therapy among those individuals already suffering from an anxiety disorder.

Rather than blocking the chemical to prevent the formation of a traumatic memory after an event,  activating BDNF at the time of therapy for an existing disorder might make the therapy work better, Ressler said.  It's an emotion-enhancing molecule, but you have to be careful about what emotions you are enhancing.

To prevent and/or treat these disorders, Ressler believes that scientists must understand the genetics and neurobiology that control emotions and emotional learning. It's a very exciting time, as the fields of learning and memory, and our understanding of neural systems, are converging, Ressler said.  We may one day be able to direct the formation of emotional memories in a way that will be much more helpful to our patients.    

The work, which was  recently published online in the Proceedings of the National Academy of Sciences, was funded by the National Science Foundation, the National Institutes of Health, the National Alliance for Research on Schizophrenia and Depression and the Burroughs Wellcome Fund.

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