The brain is very good at alerting us to threats—and it is also adept at letting us know when a threat no longer exists. Sometimes this system fails, however, and unpleasant associations stick around—a malfunction thought to be at the root of post-traumatic stress disorder (PTSD). New research has identified a neuronal circuit responsible for the brain's ability to purge bad memories, findings that could have implications for treating a broad range of anxiety disorders, including PTSD.
Previous work has consistently implicated two areas of the brain as contributing to and regulating fear responses. The amygdala is involved in emotional reactions, and it flares with activity when we are scared. The prefrontal cortex steps in to calm us down when a particular threat turns out to be harmless. A large body of work implicates the two areas in fear memory, but because of their connections to many other parts of the brain, it was unknown whether their joint effort was truly at the root of overcoming fear. The new study, led by Andrew Holmes of the National Institute on Alcohol Abuse and Alcoholism, confirms that a working connection between the two brain regions is necessary to do away with fearful associations.
The researchers worked with mice trained to fear a sound paired with a foot shock. Typically if such mice are later exposed to the repeated sound without a foot shock, they will learn that the noise is harmless and will stop being afraid. In the new study, the researchers disrupted the mice's amygdala–prefrontal cortex connection using optogenetics, which controls specific neurons with fiber-optic lights. The authors found that disrupting this key connection prevented the mice from overcoming the negative association with the benign tone—they continued to fear the sound long after the foot shocks disappeared. They also discovered that the opposite was true: stimulating the circuit resulted in faster extinction of fearful memories.
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As Holmes explains, the amygdala and prefrontal cortex are two major hubs in a complex communications network. In the case of impaired fear extinction such as PTSD, however, it appears that just the one connection between the two regions is faulty, not the hubs themselves. As such, the efforts of previous experiments to treat PTSD by altering activity in one of these major brain areas have probably been overkill.
The new finding suggests that researchers should explore medications that act on this specific fear circuit. Holmes believes that healthy fear extinction relies on “neural plasticity,” the brain's ability to make new neuronal connections, which is in part influenced by the brain's native cannabinoids, compounds that regulate neurotransmitters. Drugs that alter the cannabinoid system, such as THC, the active component in marijuana, could temporarily make the fear circuit more plastic—perhaps allowing clinical techniques, such as exposure therapy, to better alleviate anxiety.
