Researchers Identify Neural Switch for Animal Freeze-or-Flight Response

Leuven, Belgium, July 23, 2025 – A groundbreaking study conducted by an international team of researchers has unveiled a significant neural switch that dictates whether animals instinctively flee from threats or freeze in place. This discovery provides crucial insights into the evolutionary adaptations of species' survival mechanisms based on their environments.

The research, published in the prestigious journal *Nature*, highlights the findings from comparative studies between two closely related species of deer mice: the forest mouse (*Peromyscus maniculatus*) and the open-field mouse (*Peromyscus polionotus*). The study reveals that the activation of a specific brain region, the dorsal periaqueductal gray (dPAG), is central to determining the escape behaviors of these animals.

Felix Baier, a co-first author and member of the research team at Harvard University, stated, "To precisely measure escape behavior, we presented both types of mice with stimuli resembling potential aerial predators in a controlled setting. Our findings indicated that open-field mice required nearly double the intensity of stimulus to trigger an escape compared to their forest-dwelling relatives. This suggests significant differences in how these species process threat stimuli."

The study employed advanced neural recording techniques, including Neuropixels probes, to analyze how the dPAG functions in response to perceived threats. The researchers discovered that, while both species detect impending danger similarly, their responses diverge significantly when it comes to action. In forest mice, the dPAG immediately initiates an escape response, while in open-field mice, this command is notably absent, necessitating a higher stimulus threshold to elicit a flight response.

Katja Reinhard, another co-first author and former postdoctoral researcher at imec, KU Leuven, commented on the implications of the findings. "Our research illustrates that evolution can modify central brain regions, rather than merely adjusting peripheral sensory inputs, to alter behavior. This indicates an evolutionary repurposing of neural circuits to fine-tune survival responses."

The research team further demonstrated a causal relationship between dPAG activity and behavioral responses. By artificially stimulating dPAG neurons in forest mice, they induced escape behaviors even in the absence of threats. Conversely, dampening dPAG activity raised the escape threshold, mimicking the behavior of the open-field cousins.

This study sheds light on the neurological underpinnings of instinctive behaviors, emphasizing the brain's flexibility in adapting to environmental demands. Lead authors, Professor Karl Farrow from imec, KU Leuven, and Professor Hopi Hoekstra from Harvard University, remarked on the significance of their discoveries. Farrow said, "By studying these two related species, we uncovered a switch that balances freeze versus flight, demonstrating how natural selection fine-tunes behavior without needing to rewire the sensory systems."

Hoekstra added, "Our findings underscore a fundamental principle of evolution: natural selection often optimizes existing neural circuits rather than creating entirely new pathways."

The study was supported by numerous grants, including those from the Howard Hughes Medical Institute, the European Union's Horizon 2020 program, and the National Institutes of Health (NIH). As researchers continue to explore the intricacies of animal behavior, these findings pave the way for a deeper understanding of survival instincts and evolutionary biology.

In conclusion, the identification of this neural switch not only enhances knowledge about animal behavior but also opens avenues for future research into the neurological mechanisms governing instinctive reactions in various species. Understanding these processes may lead to broader applications in fields such as neuroscience, psychology, and conservation biology.