Researchers at the Sainsbury Wellcomo Center (SWC) in UCL have presented the precise brain mechanisms that allow animals to overcome instinctive fears. Posted today in ScienceThe study in mice could have implications to develop therapies for fear -related disorders such as phobias, anxiety and post -traumatic stress disorder (PTSD).
The research team, led by Dr. Sara Mederos and Professor Sonja Hofer, mapped how the brain learns to suppress the responses to the perceived threats that are harmless over time.
“Humans are born with instinctive fear reactions, as responses to strong noises or rapid coupling objects,” explains Dr. Mederos, a researcher in the Hofer laboratory on SWC. “However, we can cancel these instinctive responses through experience, such as children who learn to enjoy fireworks instead of fearing their strong bangs. We wanted to understand the brain mechanisms that underlie such forms of learning.”
Using an innovative experimental approach, the team studied mice presented with an expanding shadow that imitated an air predator that was approaching. Initially, the mice sought refuge in finding this visual threat. However, with a repeated exposure and without real danger, mice learned to remain calm instead of escaping, providing researchers with a model to study the suppression of fear responses.
Based on previous works in Hofer’s laboratory, the team knew that an area of the brain called ventrolateral geniculate (VLGN) could suppress fear reactions when it was active and could track the knowledge of the previous threat experience. The VLNG also receives strong contributions from visual areas in the cerebral cortex, so the researchers explored if this neural route had a role in learning not to fear a visual threat.
The study revealed two key components in this learning process: (1) specific regions of the visual cortex proved to be essential for the learning process, and (2) a brain structure called ventrolateral geniculate (VLGN) stores these memories induced by the learning.
“We discovered that animals did not learn to suppress their fear responses when specific cortical visual areas were inactivated.
“Our results challenge traditional opinions about learning and memory,” says Professor Hofer, lead author of the study. “While the cerebral cortex has long been considered the main center of the brain for learning, memory and flexibility of behavior, we find that subcortical VLGN and not the visual cortex really stores these crucial memories. This neural route can provide A link between cognitive neocortical processes and “ behaviors mediated by the cable trunk, allowing animals to adapt instinctive behaviors. “
The researchers also discovered the cellular and molecular mechanisms behind this process. Learning occurs through the increase in neuronal activity in specific VLGN neurons, triggered by the release of endocannabinoids, internal messenger molecules that are known to regulate mood and memory. This release decreases inhibitory entry to VLGN neurons, resulting in greater activity in this area of the brain when the visual threat stimulus is located, which suppresses fear responses.
The implications of this discovery extend beyond the laboratory. “Our findings could also help advance our understanding of what is going wrong in the brain when the regulation of response to fear is affected in conditions such as phobias, anxiety and PTSD. While instinctive reactions of the fear of predators can Being less relevant to modern humans, the brain path we also discover in humans, “explains Professor Hofer. “This could open new ways to treat fear disorders in directing Vlgn circuits or localized endocannabinoid systems.”
The research team now plans to collaborate with clinical researchers to study these brain circuits in humans, hoping to develop new and specific treatments for fear responses and anxiety disorders.
This investigation was funded by the central subsidy of the Sainsbury WellCome Center for the GATSBY Charity Foundation and Wellcom (090843/F/09/Z); an award to the researcher Wellcome (219561/Z/19/Z); A Postdoctoral Scholarship (EMPO ALTF 327-2021) and an Early Carrera Wellcoma Award (225708/Z/22/Z).