In recent years, our understanding of the neural processes that underpin persistent fear and anxiety have increased dramatically, yet treatment for these common psychiatric conditions remains poor. For some individuals, repeated exposure to a fearful situation or stimulus can gradually help uncouple the trigger from the anxiety response, but what goes on in the brain during this process remains hazy.
Now, scientists think that they may have a better idea, with the discovery of a circuit that aids the generation of new memories that displace the older, fearful ones. This particular pathway joins two distinct brain areas involved in decision making and the processing of emotions, including fear and anger.
Although the study was conducted in mice, the findings are likely not species-specific given that this network displays functional similarities between rodents and humans. So if the findings are indeed translatable, scientists may be able to use them to help treat individuals with anxiety and trauma-related disorders. The study has been published inScience Advances.
The evolution of defense systems to help an animal to cope with dangerous situations has been pivotal to species’ success throughout history as, by preparing for future threats that could arise, they help to promote survival. But while important, memories of traumatic or fearful experiences can sometimes linger, promoting the development of psychiatric conditions like anxiety and post-traumatic stress disorder when a certain trigger is persistently associated with an unpleasant past experience.
While unfortunately we cannot erase bad memories at will, techniques such as exposure therapy have demonstrated that it is at least possible to replace “fear” memories with newer, more positive ones, a mechanism known as memory extinction. Studies have demonstrated that extinguishing fear is more successful in rodents displaying high levels of activity in two key brain regions, the ventromedial prefrontal cortex (vmPFC) and theamygdala. The former is involved in decision making and the inhibition of emotion, whereas the latter helps us to process emotions and determine which memories the brain stores.
This suggested that a circuit connecting these two regions could assist the formation of so-called extinction memories, so researchers devised an experiment to find out more. They started off by using a virus to insert genes for light-sensitive proteins into the brains of mice, or, more specifically, the neurons that connect the vmPFC with the amygdala. This meant that through the use of implanted optical fibers, the researchers could selectively activate this circuit on demand.
The team then conditioned mice to associate a particular noise with a small shock to the foot, which successfully evoked fear whenever the sound was played. The following day, the researchers repeatedly exposed the animals to the same tone while stimulating their target brain circuit using light. Compared with control mice without the light treatment, these animals were found to be much better at creating extinction memories. And when they repeated the experiment using light to inhibit, rather than to stimulate, the vmPFC-amygdala circuit, the mice were impaired in their ability to form extinction memories.
These findings could have important implications if they are translatable to humans, as one day it may be possible to pharmacologically boost the activity of this circuit in individuals with post-traumatic stress disorder or other anxiety disorders, which could potentially help to boost the formation of helpful extinction memories during treatment.