Neuroscientists at the Sainsbury Wellcome Centre (SWC) at University College London have uncovered a neural mechanism in mice that enables them to overcome instinctive fears, revealing the precise regions of the brain that suppress fear responses. The study was led by Dr. Sara Mederos and Professor Sonja Hofer.
Initially, naïve mice fled to a shelter when presented with a looming visual threat, such as an overhead expanding shadow simulating a predatory bird's swoop. The threat consisted of three consecutive expanding black spots over three seconds, a well-established measure inducing instinctive fear and escape behavior. However, over time, the mice learned to stop escaping from the perceived threat, demonstrating their ability to suppress instinctive fear responses after learning the stimulus was harmless.
The researchers explored the role of the ventrolateral geniculate nucleus (vLGN) in learning to overcome fear responses, building on previous findings that it can modulate instinctive fear and track prior threat knowledge. The team mapped how the brain learns to suppress responses to perceived threats that prove harmless over time, demonstrating that the memory of this suppression is stored in the vLGN.
"However, we can override these instinctive responses through experience, like when children learn to enjoy fireworks instead of fearing their noise. We wanted to understand the brain mechanisms underlying these forms of learning," explained Mederos. She added that humans are born with instinctive fear reactions, such as responses to loud noises or rapidly approaching objects.
The study discovered two key components in the learning process: specific regions of the visual cortex are essential for initial learning, and the vLGN stores memories induced by this learning. Learning occurs through increased neural activity in specific vLGN neurons, which suppresses fear responses.
The researchers uncovered the cellular and molecular mechanisms behind the learning process. They found that the release of endocannabinoids decreases inhibitory input to vLGN neurons, leading to greater activity in this area of the brain when the visual threat stimulus is present, which suppresses fear responses. Endocannabinoids are internal messenger molecules in the brain known to regulate mood and memory.
This understanding could lead to therapies targeting the vLGN circuits or localized endocannabinoid systems for treating maladaptive fear responses and anxiety disorders such as phobias, anxiety, and post-traumatic stress disorder (PTSD), which affect over 300 million people worldwide.
"Our findings could also 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," said Hofer, according to Genetic Engineering and Biotechnology News.
The study focused on mice, but the team believes something similar is likely occurring in the human brain, as the same brain pathway exists in humans. The research team is planning to collaborate with clinical researchers to study these brain circuits in humans. They hope to develop new, targeted treatments for maladaptive fear responses and anxiety disorders.
By identifying key brain areas involved in fear suppression, the study highlights potential targets for therapeutic interventions, such as deep brain stimulation (DBS), focused ultrasound, or pharmacological approaches targeting endocannabinoid receptors to treat fear-related disorders like post-traumatic stress disorder and anxiety.
This research sheds light on how the mammalian brain learns to remain calm in the face of an unfounded threat, mapping the mechanisms in the visual cortex and the ventrolateral geniculate nucleus (vLGN) that store memories induced by learning. The findings could have implications for developing therapeutics for fear-related disorders such as phobias, anxiety, and PTSD.
The article was written with the assistance of a news analysis system.