Summary: A new study reveals how evolution sharpens instinctive fear responses by adjusting a single neural switch deep in the brain. By comparing two closely related deer-mouse species, researchers show that mice from dense forests have an over-sensitive escape circuit, while open-field mice are more prone to freeze when faced with the same threat.
That behavioral difference is traced to the dorsal periaqueductal gray (dPAG), a central brain hub for defensive actions. In forest-dwelling mice the dPAG is more easily triggered, producing rapid flight; in open-field mice the dPAG is less likely to issue a run command, favoring freezing instead. The findings illustrate how natural selection refines survival behavior by tuning existing brain pathways rather than creating new ones.
Key facts
- Neural switch identified: Sensitivity of the dPAG determines whether an animal flees or freezes.
- Species difference: Forest mice (Peromyscus maniculatus) escape quickly; open-field mice (Peromyscus polionotus) tend to freeze.
- Evolutionary insight: Behavioral adaptation arises from changes in central circuitry downstream of sensory inputs, not from altered sensory perception.
Researchers
An international team from institutions in Belgium and the United States compared two sister species of deer mice to discover how instinctive defensive choices are tuned to different habitats. Their results were published in Nature.

Flee or freeze?
When a predator appears, animals must pick an appropriate defensive action in a split second. In a cluttered forest, running into cover usually improves survival; on open grassland, staying still and hidden is often safer. The researchers asked how evolution solves this trade-off without overhauling the whole nervous system.
To measure escape behavior precisely, the team presented both species with controlled stimuli that mimicked an aerial predator. They found that open-field mice consistently required roughly twice the stimulus intensity to trigger escape compared with forest mice, indicating a major difference in how the threat translates into action.
A switch in the brain
Using advanced neural recordings (Neuropixels probes) and targeted manipulations, the researchers localized the behavioral divergence to the dorsal periaqueductal gray (dPAG), a compact group of neurons deep in the midbrain that issues motor commands for escape.
Both species detect the looming stimulus similarly — sensory pathways from the eye to upstream brain regions respond comparably when the animals do not act. The difference appears downstream: in forest mice, looming stimuli often trigger a fast, high-amplitude dPAG signal that correlates with immediate acceleration and flight. In open-field mice, dPAG activity does not scale with movement in the same way and seldom issues the run command, so these mice default to freezing.
The team tested causality by manipulating dPAG neurons. Activating dPAG cells in forest mice could provoke escape even without a predator-like stimulus. Chemogenetic suppression of dPAG activity raised the escape threshold in those mice, delaying flight onset and producing behavior more like the open-field species. These interventions demonstrate that dPAG sensitivity is sufficient and necessary for the species-specific differences in defensive strategy.
Built-in flexibility and evolutionary principle
The study highlights the brain’s flexibility: evolution can retune a central circuit node to shift behavioral priorities across environments without changing peripheral sensory encoding. As the authors note, this is an economical evolutionary strategy — tweaking an internal switch to produce different outcomes from the same inputs.
Lead investigators emphasize that their findings reveal a general principle in evolutionary neuroscience: adaptive behaviors often arise from modifications to existing neural circuits rather than the construction of entirely new pathways. Comparing closely related species uncovered how a conserved architecture can be repurposed to meet distinct ecological demands.
Funding
Work at the VIB-KU Leuven Center for Brain and Disease Research was supported by multiple fellowships and grants, including the HHMI International Student Research Fellowship, the American Society of Mammalogy, the Herchel Smith and Robert A. Chapman memorial scholarships, fellowships from Harvard, the European Union’s Horizon 2020 and Marie Skłodowska-Curie programs, FWO, ERC, NIH, and the Howard Hughes Medical Institute.
About this research news
Author: Joran Lauwers
Source: VIB
Contact: Joran Lauwers – VIB
Image: The image is credited to Neuroscience News
Original research (open access): “The neural basis of species-specific defensive behaviour in Peromyscus mice” by Katja Reinhard et al., published in Nature. The study maps species-specific escape thresholds to a central midbrain circuit node, showing that differences in dPAG activity explain divergent freeze-versus-flight strategies in two Peromyscus species.
Abstract (summary)
Escaping an imminent predator is critical for survival, and closely related species can adopt different defensive strategies. Two sister species of deer mice respond differently to the same looming stimulus: forest specialists (Peromyscus maniculatus) predominantly escape, while an open-field specialist (Peromyscus polionotus) briefly freezes. This behavior stems from species-specific escape thresholds that are largely independent of context and can be triggered by visual or auditory cues. Although both species activate the superior colliculus in response to visual threat, the dorsal periaqueductal gray (dPAG) plays different roles: in P. maniculatus dPAG activity scales with running speed and drives escape, whereas in P. polionotus dPAG activity correlates poorly with movement. Optogenetic and chemogenetic experiments confirm that dPAG activation elicits acceleration in forest mice and that inhibiting dPAG delays escape, matching the open-field response. Together, these findings localize an ecologically relevant behavioral difference to a specific central circuit node downstream of peripheral sensory neurons.