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Scientists have discovered a fascinating way the brain learns to overcome instinctual fears, shedding light on how we adapt to perceived threats over time. The discovery could pave the way for new treatments for fear-related disorders such as post-traumatic stress disorder and anxiety, using the brain's own mechanisms to unlearn irrational fears.
Unraveling the mechanism of fear suppression in the brain
Scientists from the Sainsbury Wellcome Centre (SWC) at UCL have identified brain mechanisms that help animals overcome instinctive fears. Their research, published today (6 February) in the journal Science, investigates how mice learn to suppress fear in response to perceived threats that turn out to be harmless. These findings could help develop treatments for fear-related conditions such as phobias, anxiety, and post-traumatic stress disorder (PTSD).
Led by Dr. Sarah Mederos and Professor Sonya Hofer, the research team identified how the brain adapts to fear, learning to suppress responses to perceived threats that eventually turn out to be harmless.
How experience overcomes instinctive fear
"Humans are born with instinctive fear responses, such as responding to loud noises or rapidly approaching objects," explains Dr. Mederos, a research scientist in the Hofer lab at SWC. "However, we can override these instinctive responses through experience—for example, children learn to enjoy fireworks rather than fear their loud explosions. We wanted to understand the brain mechanisms that underlie these forms of learning."
Using an innovative experimental approach, the team studied mice presented with an expanding shadow overhead that mimicked the approach of an aerial predator. Initially, the mice sought refuge when faced with this visual threat. However, when re-exposed and in the absence of real danger, the mice learned to remain calm instead of fleeing, providing the researchers with a model for studying the suppression of fear responses.
The brain's powerhouse that regulates fear
Based on previous work in Hofer's lab, the team knew that a brain region called the ventrolateral geniculate nucleus (vLGN) can suppress fear responses when active and was able to track knowledge of prior threat experience. The vLGN also receives strong input from visual areas in the cerebral cortex, so the researchers investigated whether this neural pathway plays a role in learning not to fear visual threat.
The study identified two key components of this learning process: (1) certain areas of the visual cortex have been shown to be important for the learning process, and (2) a brain structure called the ventrolateral geniculate nucleus (vLGN) stores these memories induced by learning.
"We found that animals did not learn to suppress their fear responses when certain cortical visual areas were inactivated. However, once the animals had already learned to stop fleeing, the cerebral cortex was no longer needed," explained Dr. Mederos.
Rethinking how the brain stores fear memories
"Our results challenge traditional views of learning and memory," says Professor Hofer, senior author of the study. "Although the cerebral cortex has long been considered the main center for learning, memory and behavioral flexibility, we found that these important memories are actually stored in the subcortical vLGN, not the visual cortex. This neural pathway may provide a link between cognitive neocortical processes and 'hardwired' behaviors mediated by the brainstem, allowing animals to adapt instinctive behaviors."
The researchers also uncovered the cellular and molecular mechanisms behind this process. Learning occurs through increased neuronal activity in specific vLGN neurons, triggered by the release of endocannabinoids, molecules within the brain that regulate mood and memory. This release reduces the inhibitory influence on vLGN neurons, leading to increased activity in this brain region when a visual threat stimulus is encountered, which suppresses fear responses.
Implications for the treatment of anxiety and post-traumatic stress disorder
The implications of this discovery extend beyond the laboratory. "Our findings may also help us better understand what goes wrong in the brain when the regulation of the fear response is disrupted in conditions such as phobias, anxiety and post-traumatic stress disorder. Although instinctive fear responses to predators may be less relevant to modern humans, the brain pathway we have identified also exists in humans," explains Professor Hofer. "This may open up new avenues for treating fear disorders by targeting vLGN circuits or localized endocannabinoid systems."
The research team now plans to collaborate with clinical researchers to study these brain circuits in humans with the hope of one day developing new targeted treatments for maladaptive fear responses and anxiety disorders.
