Neuroscience Breakthrough: Key Neural Switch Controls Flee or Freeze Response

In a groundbreaking study published in *Nature*, researchers from Belgium and the United States have identified a critical neural switch in the brains of deer mice that determines whether the animals instinctively flee from or freeze in response to threats. The study, led by Professors Karl Farrow of imec and VIB at KU Leuven and Hopi Hoekstra of Harvard University, sheds light on the evolutionary adaptations that fine-tune animal responses based on their environment.

The research team conducted a comparative analysis of two closely related deer mouse species: the forest mouse (*Peromyscus maniculatus*) and the open-field mouse (*Peromyscus polionotus*). Through controlled experiments mimicking predator presence, they found that forest mice reacted to aerial threats with immediate escape, while open-field mice exhibited a freezing behavior. This disparity in response was traced to variations in the activation of the dorsal periaqueductal gray (dPAG), a brain region critical for coordinating escape behaviors.

According to Felix Baier, co-first author and part of the research team, "Open-field mice required approximately twice the intensity of stimulus to trigger an escape response compared to their forest counterparts, indicating significant differences in threat processing."

The study also revealed that both species perceive threats similarly; however, the activation of the dPAG differed markedly when it came to executing escape behaviors. Baier noted, “While both species register the looming threat identically, the command to escape was instantaneous in forest mice, whereas open-field mice did not receive such commands.”

Advanced neural recording techniques allowed the researchers to establish a causal link between the dPAG's activation and the mice's behavior. When researchers artificially stimulated neurons in the dPAG of forest mice, these animals would attempt to flee even without a perceived threat. Conversely, dampening dPAG activity raised their escape threshold, aligning their behavior closer to that of the open-field mice.

The implications of this study extend beyond the immediate understanding of instinctive behaviors. The authors argue that it demonstrates how evolutionary processes can fine-tune existing neural circuits to adapt behaviors without the need for completely new pathways. As Professor Farrow explained, "Natural selection often refines existing neural architectures rather than constructing entirely new ones."

This discovery not only enhances knowledge of animal behavior but also contributes to broader neuroscientific discussions regarding how flexibility in neural circuits can influence survival strategies in fluctuating environments. The research underscores a fundamental principle of evolutionary biology: adaptation often involves subtle adjustments rather than wholesale redesigns of biological systems.

In light of these findings, future research may explore further implications for understanding human responses to threats and stress, potentially informing therapeutic approaches for anxiety disorders and PTSD. Understanding the neural mechanisms that govern these instinctual responses in animals may provide insights into similar processes in humans, where the balance between flight and freeze responses is crucial for survival.

The study, which exemplifies the intersection of evolutionary biology and neuroscience, opens new avenues for research into the adaptability of neural circuits and the evolutionary pressures shaping behavior across species.

Source: Vlaams Instituut voor Biotechnologie. Baier, F., et al. (2025). The neural basis of species-specific defensive behaviour in Peromyscus mice. *Nature*. doi.org/10.1038/s41586-025-09241-2.