Neuroscientists discover how the brain overcomes fear

Animals rely on instinctive behaviors to respond quickly to threats and opportunities. These automatic reactions, crucial for survival and reproduction, are typically controlled by brainstem circuits that function independently of higher brain processes.

However, adapting these behaviors to new environments is just as important as having them. Suppressing outdated instinctive responses allows animals to conserve energy, avoid unnecessary risks, and take advantage of new opportunities.

Fear responses, such as escaping from an overhead shadow that mimics a predator, are among the most essential instinctive reactions. These reflexes are driven by neural circuits in the medial superior colliculus and periaqueductal gray, which process visual threats and trigger immediate escape behaviors.

While these reactions are hardwired, animals can learn to suppress them when they realize a perceived threat is harmless. This process involves more complex neural circuits beyond the brainstem, particularly those in the neocortex.

Researchers at the Sainsbury Wellcome Centre (SWC) at University College London explored how animals override instinctive fear. Their study, published in Science, focused on how mice learned to remain calm when repeatedly exposed to a looming shadow that initially triggered an escape response.

“Humans are born with instinctive fear reactions, such as responses to loud noises or fast-approaching objects,” explains Dr. Sara Mederos, a research fellow in the Hofer Lab at SWC. “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.”

To study this, researchers used an innovative approach where mice were placed in an arena with a shelter and exposed to an overhead expanding shadow. Initially, the mice instinctively escaped to the shelter. Over time, as they repeatedly encountered the shadow without experiencing harm, they learned to suppress their escape response. This model provided insight into how the brain regulates instinctive fear.

The team identified two critical components in this learning process. First, higher visual areas (HVAs) in the cerebral cortex, particularly regions called posterolateral HVAs (plHVAs), were essential for learning to suppress fear responses. Second, the ventrolateral geniculate nucleus (vLGN), a structure deep in the brain, played a key role in storing these learned fear suppressions.

The vLGN, located in the prethalamus, is primarily composed of inhibitory neurons and acts as a control center for instinctive behaviors. It receives direct input from the retina and is capable of suppressing fear responses to visual threats. This study revealed that the vLGN also receives strong input from the visual cortex, suggesting a link between cognitive processes and instinctive behaviors.

The researchers tested this by temporarily disabling the plHVAs in mice using optogenetics, a technique that controls neural activity with light. When plHVAs were silenced during the learning phase, mice continued to escape from the visual stimulus, failing to learn that it was harmless. However, once learning had occurred, disabling the plHVAs had no effect, meaning the visual cortex was necessary for learning but not for maintaining the learned suppression of fear.

Professor Sonja Hofer, senior author of the study, highlights the significance of this finding: “Our results challenge traditional views about learning and memory. While the cerebral cortex has long been considered the brain’s primary center for learning, memory, and behavioral flexibility, we found that the subcortical vLGN, rather than the visual cortex, actually stores these crucial memories.”

This discovery suggests that while the cortex is responsible for processing and evaluating threats, the vLGN acts as a long-term storage center for learned fear suppressions. Essentially, the cortex instructs the vLGN to override instinctive fear reactions once an animal learns that a perceived threat is not dangerous.

Beyond its impact on neuroscience, this research could have implications for treating anxiety disorders, phobias, and post-traumatic stress disorder (PTSD). Maladaptive fear responses, where individuals continue to react strongly to non-threatening stimuli, are a hallmark of these conditions. By understanding how the brain suppresses instinctive fear, researchers may uncover new therapeutic targets.

The study found that learning-induced suppression of fear is linked to increased neural activity in specific vLGN neurons, triggered by the release of endocannabinoids. These naturally occurring molecules regulate mood and memory by altering inhibitory inputs to the vLGN. When endocannabinoids were released, the vLGN became more active, suppressing fear responses.

“These findings could help advance our understanding of what is going wrong in the brain when fear response regulation is impaired in conditions such as phobias, anxiety, and PTSD,” says Professor Hofer. “While instinctive fear reactions to predators may be less relevant for modern humans, the brain pathway we discovered exists in humans too. This could open new avenues for treating fear disorders by targeting vLGN circuits or local endocannabinoid systems.”

The research team now plans to collaborate with clinical researchers to study these brain circuits in humans. Their goal is to develop targeted treatments for anxiety disorders by modulating the vLGN and related neural pathways.

By identifying the precise mechanisms underlying fear suppression, future therapies may be able to help individuals overcome excessive fear responses, improving mental health outcomes.

Note: Materials provided above by The Brighter Side of News. Content may be edited for style and length.

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