The neural basis of species-specific defensive behaviour in Peromyscus mice

Felix Baier (), Katja Reinhard, Bram Nuttin, Arnau Sans-Dublanc, Chen Liu, Victoria Tong, Julie S. Murmann, Keimpe Wierda, Karl Farrow () and Hopi E. Hoekstra ()
Additional contact information
Felix Baier: Harvard University
Katja Reinhard: Neuro-Electronics Research Flanders
Bram Nuttin: Neuro-Electronics Research Flanders
Arnau Sans-Dublanc: Neuro-Electronics Research Flanders
Chen Liu: Neuro-Electronics Research Flanders
Victoria Tong: Harvard University
Julie S. Murmann: Neuro-Electronics Research Flanders
Keimpe Wierda: VIB-KU Leuven Center for Brain and Disease Research, CBD Technologies
Karl Farrow: Neuro-Electronics Research Flanders
Hopi E. Hoekstra: Harvard University

Nature, 2025, vol. 645, issue 8080, 439-447

Abstract: Abstract Evading imminent threat from predators is critical for animal survival. Effective defensive strategies can vary, even between closely related species. However, the neural basis of such species-specific behaviours remains poorly understood1–4. Here we find that two sister species of deer mice (genus Peromyscus)5 show different responses to the same looming stimulus: Peromyscus maniculatus, which occupies densely vegetated habitats, predominantly escapes, whereas the open field specialist, Peromyscus polionotus, briefly freezes. This difference arises from species-specific escape thresholds, is largely context-independent, and can be triggered by both visual and auditory threat stimuli. Using immunohistochemistry and electrophysiological recordings, we find that although visual threat activates the superior colliculus in both species, the role of the dorsal periaqueductal grey (dPAG) in driving behaviour differs. Whereas dPAG activity scales with running speed in P. maniculatus, neural activity in the dPAG of P. polionotus correlates poorly with movement, including during visually triggered escape. Moreover, optogenetic activation of dPAG neurons elicits acceleration in P. maniculatus but not in P. polionotus, and their chemogenetic inhibition during a looming stimulus delays escape onset in P. maniculatus to match that of P. polionotus. Together, we trace species-specific escape thresholds to a central circuit node, downstream of peripheral sensory neurons, localizing an ecologically relevant behavioural difference to a specific region of the mammalian brain.

Date: 2025
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DOI: 10.1038/s41586-025-09241-2

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