The neural basis of species-specific defensive behaviour in Peromyscus mice
Baier F, Reinhard K, Nuttin B, Sans-Dublanc A, Liu C, Tong V, Murmann JS, Wierda K, Farrow K, Hoekstra HE. 2025. The neural basis of species-specific defensive behaviour in Peromyscus mice. Nature.
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Author
Baier, Felix;
Reinhard, Katja;
Nuttin, Bram;
Sans-Dublanc, Arnau;
Liu, Chen;
Tong, Victoria;
Murmann, Julie StefanieISTA;
Wierda, Keimpe;
Farrow, Karl;
Hoekstra, Hopi E.
Department
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 understood1,2,3,4. 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.
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Date Published
2025-07-23
Journal Title
Nature
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Springer Nature
Acknowledgement
The authors thank M. Yilmaz, M. Meister, M. Joesch and T. Branco for advice on the behavioural experiments; C. Dulac, V. Bitsikas, E. Diel and J. Chen for advice on the immunohistochemistry and RNAscope experiments; J. Greenwood and E. Soucy for technical and engineering help; A. Chrzanowska for help and advice on optogenetic experiments; A. Calzoni for help aligning histological sections to a brain atlas; S. Worthington for statistical advice; P. Gonçalves for advice with the electrophysiology analysis; I. Vlaemick for help with whole cell experiments; R. Hellmiss for figure design; B. Sabatini, V. Stempel, K. Tyssowski and N. Sanguinetti for feedback on the manuscript; and Y. M. Lee and A. Tomcho for photos of P. maniculatus and P. leucopus habitats (Fig. 1). F.B. was supported by an HHMI International Student Research Fellowship, a Grant-in-Aid of the American Society of Mammalogy, a Herchel Smith Graduate Fellowship, a Robert A. Chapman Memorial Scholarship, and a Joan Brockman Williamson Fellowship. This project received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement 665501 and by the FWO (12S7917N and 12S7920N) to K.R. and from European Research Council (ERC) (grant agreement 101075848) to K.R. V.T. was supported by a Harvard PRISE fellowship and a Harvard Museum of Comparative Zoology grant for undergraduate research. K.F. is supported by the FWO (G094616N and G091719N) and the NIH (1R01EY032101). This work was supported by the Howard Hughes Medical Institute, of which H.E.H. was an Investigator.
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Cite this
Baier F, Reinhard K, Nuttin B, et al. The neural basis of species-specific defensive behaviour in Peromyscus mice. Nature. 2025. doi:10.1038/s41586-025-09241-2
Baier, F., Reinhard, K., Nuttin, B., Sans-Dublanc, A., Liu, C., Tong, V., … Hoekstra, H. E. (2025). The neural basis of species-specific defensive behaviour in Peromyscus mice. Nature. Springer Nature. https://doi.org/10.1038/s41586-025-09241-2
Baier, Felix, Katja Reinhard, Bram Nuttin, Arnau Sans-Dublanc, Chen Liu, Victoria Tong, Julie Stefanie Murmann, Keimpe Wierda, Karl Farrow, and Hopi E. Hoekstra. “The Neural Basis of Species-Specific Defensive Behaviour in Peromyscus Mice.” Nature. Springer Nature, 2025. https://doi.org/10.1038/s41586-025-09241-2.
F. Baier et al., “The neural basis of species-specific defensive behaviour in Peromyscus mice,” Nature. Springer Nature, 2025.
Baier F, Reinhard K, Nuttin B, Sans-Dublanc A, Liu C, Tong V, Murmann JS, Wierda K, Farrow K, Hoekstra HE. 2025. The neural basis of species-specific defensive behaviour in Peromyscus mice. Nature.
Baier, Felix, et al. “The Neural Basis of Species-Specific Defensive Behaviour in Peromyscus Mice.” Nature, Springer Nature, 2025, doi:10.1038/s41586-025-09241-2.
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