Fear may blur the line between danger and safety, mouse study finds

Fear may make the brain less able to tell danger from safety, not more, according to research in mice. The finding offers a possible explanation for the intense fear responses seen in anxiety and post-traumatic stress disorder (PTSD).

For years, scientists believed fear helped the brain sharpen the difference between threatening and harmless experiences. A study led by researchers at the Douglas Research Centre at McGill University and the University of Toronto-Scarborough challenges that assumption. The findings were published in Nature Neuroscience.

In the experiments, 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’ brain activity began to show overlapping patterns. The brain’s representations of safe and dangerous experiences became less distinct.

“Our findings suggest fear may blur the boundary between danger and safety rather than sharpen it,” said senior author Mark Brandon, Associate Professor in McGill’s Department of Psychiatry and Researcher at the Douglas. “This could reshape how scientists think about anxiety and PTSD.”

Watching the brain process fear

To investigate how these changes occur, the team built an unusual experimental setup combining augmented reality with real-time brain imaging. Mice could be virtually “teleported” between environments associated with danger and safety. By changing the sights and sounds around the animals, scientists could make them experience different settings without physically moving them.

At the same time, miniature microscopes monitored hundreds of neurons in the hippocampus, a brain region essential for learning and memory. This let the team observe how brain activity changed as the mice moved between experiences linked to safety and threat.

“That gave us something conventional fear conditioning experiments cannot easily provide: a moment-by-moment view of the brain switching between competing maps of dangerous and safe memories,” said Robert Rozeske, Assistant Professor in University of Toronto’s Department of Psychology and lead author on the publication.

Why the brain may confuse safety with danger

Although mixing memories of safe and dangerous experiences might seem like a problem, the researchers believe it could serve an evolutionary purpose. The experiments suggested that overlapping memory representations allowed the brain to retrieve information about previous threats more rapidly, helping an animal recognize possible danger and respond before it is too late.

That strategy comes with 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 unnecessarily to a false alarm may sometimes be preferable to overlooking a genuine danger.

“The ventral hippocampus may be part of a system that prioritizes a rapid ‘better safe than sorry’ response,” said Rozeske. “In other words, the brain may sacrifice precision for speed when danger matters.”

The ventral hippocampus is a part of the hippocampus involved in processing emotionally significant experiences, including fear and anxiety. The findings suggest overlapping memory representations in this region may help the brain switch rapidly into a defensive state.

A survival mechanism may help explain PTSD

The discovery could also offer insight into why people with anxiety and trauma-related disorders sometimes have powerful fear responses in situations that pose no immediate threat. For someone with PTSD, an otherwise harmless sight, sound or environment can trigger memories associated with a traumatic experience. The resulting fear can feel immediate and overwhelming, even when the person is objectively safe.

The researchers suggest such reactions may arise, at least in part, when a normally useful survival mechanism becomes excessively sensitive. Rather than reflecting a system that has simply stopped distinguishing between memories, these responses might involve a brain mechanism that shifts too quickly from recognizing safety to anticipating danger.

“Our study suggests that’s not necessarily a broken pattern-separation system, but possibly an overactive version of a normal survival mechanism gone into overdrive,” said Brandon. “That reframing could guide therapeutic approaches to address an overly fast transition to ‘danger mode’.”

Because the experiments were conducted in mice, additional research is needed to determine whether the same mechanisms contribute to anxiety and PTSD in humans. The findings nevertheless provide a new way to understand how fear influences memory, and why a brain system designed to protect against danger might sometimes generate fear when no immediate threat exists.

Study details and funding

The study, “Overlapping representations in the ventral hippocampus support rapid fear memory retrieval,” by Robert Rozeske and Mark Brandon, was published in Nature Neuroscience. The research received support from the Canadian Institutes of Health Research and the Natural Sciences and Engineering Research Council of Canada.