Freedom from fear: the role of dopamine in eliminating fear associations

The study details the role of dopamine in ensuring that rats no longer fear when they are no longer afraid

Researchers at the RIKEN Brain Science Center have discovered a circuit in the brain that is necessary to eliminate fear. The study, published in Nature Communications, details the role of dopamine in ensuring that mice no longer fear when they are no longer afraid.

Like animals, people react to conditions, especially if they involve strong negative emotions. This fact was used very well in the movie "Jaws" because the simple "da-da ... da-da" scared millions of people and nobody needed to be really chased or killed by the sharks. Normally, with the separation of conditional stimulus (music) and fearful experience (watching), the fear response will decrease over time. This is called fear extinction. When the disappearance of fear does not normally occur, it can lead to anxiety disorders such as post-traumatic stress or phobia.

To understand how the brain regulates normal and pathological conditions, the RIKEN team conducted a series of experiments on mice because they eliminated the terrible associations. They reasoned that in order for fear to disappear, the animals first need to identify when the expected terrible events do not occur. Since dopamine neurons in some parts of the brain are considered to be active when no unpleasant events are expected, the team observed dopamine neurons in a part of the brain called VTA.

After training the rats to connect specific sounds (thinking their Great White Shark music) with an abominable experience (slight footprint), the team started the extinction process. As expected, when the sounds were played multiple times without footprints, the rats stopped acting as if they were afraid of the sound. However, when the VTA dopamine neurons are silent immediately after the sound (when the rats expect their feet to be shocked), they cannot ignore the fear reaction. This indicates that there is no VTA dopamine activity at this particular time and the psychological relationship between sound and vibration cannot be eliminated.

However, what exactly did VTA dopamine activity do? This is not a simple question because not all VTA dopamine neurons are connected to the same brain area. Some are connected to brain regions because they are known for their role in the memory of extinction memory, while others are related to reward learning. Optogenetics allows the team to block each of these pathways separately, and they find that they all affect the fear fade, but in the opposite way: Block reward paths to prevent fears from subsiding, while blocking other ways to increase fear subside.

Although the results are simple, obtaining them requires technical effort. As the team leader Joshua Johansen explained, "This discovery is possible because we can manipulate dopamine neurons based on their unique brain connectivity. We used genetic and brain circuit-specific techniques, and used in anatomy. "Scientific and Cellular Populations that Control Neural Activity in Genes." Through this optogenetic setting, they were able to shine light into the brain and silence specific dopamine cell populations, suggesting their role in fear of extinction.

Now that they have discovered two dopamine pathways that can regulate fear resolution in different ways, the team is studying how to target these neurons in traditional pharmacology rather than optogenetics. Johnson said: "When used in conjunction with clinically proven behavioral therapies such as exposure therapy, pharmacology targeting the dopamine system may be an effective treatment for mental disorders such as anxiety. "To provide effective treatment for these diseases, For the treatment of mechanisms, future preclinical work will require the use of molecular strategies that can target these different groups of dopamine cells alone.