A study in mice suggests that fear may blur the brain’s distinction between danger and safety rather than sharpen it. Researchers at McGill University’s Douglas Research Center and the University of Toronto Scarborough found that neural representations of threatening and safe environments became more similar after fear learning. The findings, published in Nature Neuroscience, could offer new insight into the intense fear responses associated with anxiety and post-traumatic stress disorder (PTSD), although further research is needed to determine whether the same mechanisms operate in humans.
Fear may blur the boundary between safety and danger
Scientists have long thought that fear helps the brain distinguish threatening experiences from benign ones. However, the new study challenges that assumption.
Researchers trained mice to associate one environment with danger and another with safety. Rather than developing increasingly separate neural representations of the two locations, the animals began to show overlapping patterns of brain activity. Their representations of safe and dangerous experiences became less distinct.
“Our findings suggest that fear may blur rather than clarify the line between danger and safety,” said lead author Mark Brandon, an associate professor of psychiatry at McGill and a research fellow at Douglas University. “This could change the way scientists think about anxiety and PTSD.”
Observing the brain as mice switch between environments
To study how these changes occur, the research team developed an experimental system combining augmented reality with real-time brain imaging.
The researchers built an arena in which mice could be virtually “teleported” between environments associated with danger and safety. By changing the sights and sounds surrounding the animals, the scientists could make the mice experience different environments without physically moving them to another location.
At the same time, miniature microscopes monitored hundreds of neurons in the hippocampus, a brain region essential for learning and memory. This enabled the researchers to track changes in brain activity as the mice moved between experiences associated with safety and threat.
“This gives us something that traditional fear conditioning experiments cannot easily provide: moment-by-moment observations of the brain switching between competing maps of dangerous and safe memories,” said Robert Rozeske, an assistant professor in the Department of Psychology at the University of Toronto and lead author of the publication.
Why might the brain combine safety and danger memories?
Although overlapping representations of safe and dangerous experiences may seem problematic, the researchers believe the mechanism could have an evolutionary benefit.
The experiment suggested that combining memory representations may allow the brain to retrieve information about previous threats more quickly. This could help an animal identify possible danger and respond before it is too late.
That strategy involves a trade-off. By prioritizing speed over accuracy, the brain may react to a potential threat even when the current situation is harmless. From a survival perspective, responding to a false alarm may be less dangerous than failing to respond to a genuine threat.
“The ventral hippocampus may be part of a system that prioritizes rapid ‘better safe than sorry’ responses,” Rozeske said. “In other words, when the danger is significant, the brain may sacrifice accuracy for speed.”
The ventral hippocampus is involved in processing emotionally significant experiences, including fear and anxiety. The findings suggest that overlapping memory representations in this region may help the brain switch rapidly into a defensive state.
A possible link to anxiety and PTSD
The results may also help explain why people with anxiety and trauma-related disorders can experience strong fear responses when there is no immediate threat.
For people with PTSD, otherwise harmless sights, sounds or environments can trigger memories connected with traumatic experiences. The resulting fear may arise immediately and feel overwhelming, even when the person is objectively safe.
The researchers suggest that these reactions may occur, at least in part, when a normally useful survival mechanism becomes overly sensitive. Instead of simply reflecting a system that can no longer distinguish between different memories, the responses may involve brain mechanisms that shift rapidly from detecting safety to anticipating danger.
“Our study suggests that it is not necessarily a failure of the pattern separation system, but perhaps an overactive version of a normal survival mechanism,” Brandon said. “That reconfiguration could lead to therapeutic approaches to address the overly rapid transition to ‘danger mode.’”
Because the experiments were conducted in mice, additional research is needed to establish whether the same mechanisms contribute to anxiety and PTSD in humans. The findings nevertheless offer a new way to understand how fear affects memory and why brain systems designed to protect against danger can sometimes generate fear when no immediate threat is present.
Research details and funding
The study by Robert Rozeske and Mark Brandon, “Overlapping representations in the ventral hippocampus supports rapid fear memory retrieval,” was published in Nature Neuroscience.
The research was supported by the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.
Source: www.sciencedaily.com
