When someone is scared, the body initiates a “fight or flight” response, causing physical changes like increased breathing, rapid heartbeat, and sweating. This all helps the body to confront the threat or quickly escape from danger. Until recently, that has been about all scientists knew about overcoming fear. Now, researchers at the Sainsbury Wellcome Centre at University College London (UCL) have uncovered a precise brain mechanism that demonstrates how animals are able to overcome instinctive fears. The research, published in Science, details a study in mice that could have implications for developing therapeutics for fear-related disorders such as phobias, anxiety, and PTSD (post-traumatic stress disorder).
Dr. Sara Mederos, Professor Sonja Hofer, and their research team worked to map how the brain learns to suppress responses to perceived threats that are harmless. Dr. Mederos notes that “Humans are born with instinctive fear reactions, such as responses to loud noises or fast-approaching objects. However, we can override these instinctive responses through experience — like children learning to enjoy fireworks rather than fear their loud bangs. We wanted to understand the brain mechanisms that underlie such forms of learning.”
Using a different experimental approach, the team looked at mice that presented with an overhead expanding shadow that imitated an approaching predator. At first, the mice ran away to seek shelter when encountering the visual threat. However, after repeated exposure and realizing there was no actual danger, the mice learned to remain calm instead of escaping, providing a model to study the suppression of fear responses. Hofer Lab had been conducting previous work with an area of the brain called the ventrolateral geniculate nucleus (nLGN), where they found that this part of the brain could suppress fear reactions when active and was able to track and catalog knowledge from previous experiences of threats. The vLGN also receives strong visual input from the cerebral cortex, leading researchers to explore whether this neural pathway has a role in learning to overcome fear.
The researchers uncovered two key aspects of the learning process. First, specific regions of the visual cortex were essential in overcoming fear, and second, the brain structure of the vLGN stores these learned memories.
Professor Hofer commented that these results challenge the traditional views regarding learning and memory and states, “While the cerebral cortex has long been considered the brain’s primary centre for learning, memory and behavioural flexibility, we found the subcortical vLGN and not the visual cortex actually stores these crucial memories. This neural pathway can provide a link between cognitive neocortical processes and ‘hard-wired’ brainstem-mediated behaviours, enabling animals to adapt instinctive behaviours.”
This is not all. The team also discovered that there are cellular and molecular mechanisms behind overcoming fear. Learning occurs through increased neural activity in vLGN neurons but is triggered by the release of endocannabinoids, special brain messenger molecules that regulate mood and memory. This release results in heightened activity in the brain when a visual threat is encountered, suppressing the fear response.
The research team is now planning to collaborate with clinical researchers to study the brain circuits of humans in hopes of understanding and developing new treatments that could treat impractical fear responses and anxiety disorders.
