---
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abstract:
- lang: eng
  text: '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.'
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.
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Felix
  full_name: Baier, Felix
  last_name: Baier
- first_name: Katja
  full_name: Reinhard, Katja
  last_name: Reinhard
- first_name: Bram
  full_name: Nuttin, Bram
  last_name: Nuttin
- first_name: Arnau
  full_name: Sans-Dublanc, Arnau
  last_name: Sans-Dublanc
- first_name: Chen
  full_name: Liu, Chen
  last_name: Liu
- first_name: Victoria
  full_name: Tong, Victoria
  last_name: Tong
- first_name: Julie Stefanie
  full_name: Murmann, Julie Stefanie
  id: 1d390868-f128-11eb-9611-a0ca5f7833b5
  last_name: Murmann
- first_name: Keimpe
  full_name: Wierda, Keimpe
  last_name: Wierda
- first_name: Karl
  full_name: Farrow, Karl
  last_name: Farrow
- first_name: Hopi E.
  full_name: Hoekstra, Hopi E.
  last_name: Hoekstra
citation:
  ama: Baier F, Reinhard K, Nuttin B, et al. The neural basis of species-specific
    defensive behaviour in Peromyscus mice. <i>Nature</i>. 2025;645:439-447. doi:<a
    href="https://doi.org/10.1038/s41586-025-09241-2">10.1038/s41586-025-09241-2</a>
  apa: 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. <i>Nature</i>. Springer Nature. <a href="https://doi.org/10.1038/s41586-025-09241-2">https://doi.org/10.1038/s41586-025-09241-2</a>
  chicago: 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.” <i>Nature</i>. Springer Nature, 2025. <a href="https://doi.org/10.1038/s41586-025-09241-2">https://doi.org/10.1038/s41586-025-09241-2</a>.
  ieee: F. Baier <i>et al.</i>, “The neural basis of species-specific defensive behaviour
    in Peromyscus mice,” <i>Nature</i>, vol. 645. Springer Nature, pp. 439–447, 2025.
  ista: 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. 645, 439–447.
  mla: Baier, Felix, et al. “The Neural Basis of Species-Specific Defensive Behaviour
    in Peromyscus Mice.” <i>Nature</i>, vol. 645, Springer Nature, 2025, pp. 439–47,
    doi:<a href="https://doi.org/10.1038/s41586-025-09241-2">10.1038/s41586-025-09241-2</a>.
  short: F. Baier, K. Reinhard, B. Nuttin, A. Sans-Dublanc, C. Liu, V. Tong, J.S.
    Murmann, K. Wierda, K. Farrow, H.E. Hoekstra, Nature 645 (2025) 439–447.
date_created: 2025-08-03T22:01:31Z
date_published: 2025-07-23T00:00:00Z
date_updated: 2026-07-22T06:20:09Z
day: '23'
ddc:
- '570'
department:
- _id: GradSch
doi: 10.1038/s41586-025-09241-2
external_id:
  pmid:
  - '40702175'
file:
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page: 439-447
pmid: 1
publication: Nature
publication_identifier:
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publication_status: published
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title: The neural basis of species-specific defensive behaviour in Peromyscus mice
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  short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 645
year: '2025'
...
---
OA_place: repository
OA_type: hybrid
_id: '20883'
abstract:
- lang: eng
  text: 'Evading imminent predator threat is critical for survival. Effective defensive
    strategies can vary, even between closely related species. However, the neural
    basis of such species-specific behaviours is still poorly understood. Here we
    find that two sister species of deer mice (genus Peromyscus) show different responses
    to the same looming stimulus: P. maniculatus, which occupies densely vegetated
    habitats, predominantly escapes, while the open field specialist, P. 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 gray (dPAG) in driving behaviour
    differs. While 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 P. polionotus, while 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.'
article_processing_charge: No
author:
- first_name: Baier
  full_name: Felix, Baier
  last_name: Felix
- first_name: Katja
  full_name: Reinhard, Katja
  last_name: Reinhard
- first_name: Bram
  full_name: Nuttin, Bram
  last_name: Nuttin
- first_name: Arnau
  full_name: Sans Dublanc, Arnau
  last_name: Sans Dublanc
- first_name: Chen
  full_name: Liu, Chen
  last_name: Liu
- first_name: Victoria
  full_name: Tong, Victoria
  last_name: Tong
- first_name: Julie Stefanie
  full_name: Murmann, Julie Stefanie
  id: 1d390868-f128-11eb-9611-a0ca5f7833b5
  last_name: Murmann
- first_name: Keimpe
  full_name: Wierda, Keimpe
  last_name: Wierda
- first_name: Karl
  full_name: Farrow, Karl
  last_name: Farrow
- first_name: Hopi
  full_name: Hoekstra, Hopi
  last_name: Hoekstra
citation:
  ama: Felix B, Reinhard K, Nuttin B, et al. The neural basis of species-specific
    defensive behaviour in Peromyscus mice. 2025. doi:<a href="https://doi.org/10.5061/DRYAD.Q2BVQ83XC">10.5061/DRYAD.Q2BVQ83XC</a>
  apa: Felix, B., Reinhard, K., Nuttin, B., Sans Dublanc, A., Liu, C., Tong, V., …
    Hoekstra, H. (2025). The neural basis of species-specific defensive behaviour
    in Peromyscus mice. Dryad. <a href="https://doi.org/10.5061/DRYAD.Q2BVQ83XC">https://doi.org/10.5061/DRYAD.Q2BVQ83XC</a>
  chicago: Felix, Baier, Katja Reinhard, Bram Nuttin, Arnau Sans Dublanc, Chen Liu,
    Victoria Tong, Julie Stefanie Murmann, Keimpe Wierda, Karl Farrow, and Hopi Hoekstra.
    “The Neural Basis of Species-Specific Defensive Behaviour in Peromyscus Mice.”
    Dryad, 2025. <a href="https://doi.org/10.5061/DRYAD.Q2BVQ83XC">https://doi.org/10.5061/DRYAD.Q2BVQ83XC</a>.
  ieee: B. Felix <i>et al.</i>, “The neural basis of species-specific defensive behaviour
    in Peromyscus mice.” Dryad, 2025.
  ista: Felix B, Reinhard K, Nuttin B, Sans Dublanc A, Liu C, Tong V, Murmann JS,
    Wierda K, Farrow K, Hoekstra H. 2025. The neural basis of species-specific defensive
    behaviour in Peromyscus mice, Dryad, <a href="https://doi.org/10.5061/DRYAD.Q2BVQ83XC">10.5061/DRYAD.Q2BVQ83XC</a>.
  mla: Felix, Baier, et al. <i>The Neural Basis of Species-Specific Defensive Behaviour
    in Peromyscus Mice</i>. Dryad, 2025, doi:<a href="https://doi.org/10.5061/DRYAD.Q2BVQ83XC">10.5061/DRYAD.Q2BVQ83XC</a>.
  short: B. Felix, K. Reinhard, B. Nuttin, A. Sans Dublanc, C. Liu, V. Tong, J.S.
    Murmann, K. Wierda, K. Farrow, H. Hoekstra, (2025).
date_created: 2025-12-30T07:36:29Z
date_published: 2025-06-23T00:00:00Z
date_updated: 2026-07-22T06:20:09Z
day: '23'
department:
- _id: GradSch
doi: 10.5061/DRYAD.Q2BVQ83XC
main_file_link:
- open_access: '1'
  url: https://doi.org/10.5061/dryad.q2bvq83xc
month: '06'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
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    relation: used_in_publication
    status: public
status: public
title: The neural basis of species-specific defensive behaviour in Peromyscus mice
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2025'
...
---
OA_place: publisher
_id: '15352'
abstract:
- lang: eng
  text: "Epilepsy affects about 50 to 65 million people globally. It summarizes a
    spectrum of neurological\r\ndisorders that have in common a hyperactivity of the
    neuronal network resulting in seizures. A common\r\nassumption is that an imbalance
    between neuronal excitation and inhibition is a key mechanism in\r\nseizure generation
    and epileptogeneisis. In at least one-third of the patients, current therapies
    have\r\nproven unsuccessful in treating seizure progression. One potential reason
    could be that the therapies\r\nonly focus on neurons. Recent studies suggest that
    neuronal hyperactivity causes a microglial\r\nresponse, which reinstates brain
    homeostasis. Additionally, interactions between microglia and neurons\r\nhave
    been shown to inhibit neuronal firing and dampen seizure activity. However, the
    exact relationship\r\nbetween microglia and seizure progression in epilepsy is
    yet to be elucidated. A main bottleneck is that\r\nseveral studies investigate
    microglia dynamics in ex vivo slice models, which can severely affect the\r\nmicroglia
    dynamics due to their rapid response to environmental changes. On the other hand,
    in vivo\r\nstudies focus mostly on behavior characterization of the epileptic
    seizure phenotype and their long-term\r\nconsequences on microglia activity leaving
    out the direct consequences of acute seizure activity on\r\nmicroglia dynamics.\r\nHere,
    we perform a pilot study to combine electroencephalography (EEG) and in vivo live
    imaging to\r\ndirectly monitor and correlate the onset of seizure activity with
    microglia response. To induce seizures,\r\nwe take advantage of the kainic acid
    (KA) model, which represents similar neuropathological and\r\nelectroencephalographic
    features seen in human patients with temporal lobe epilepsy (TLE). After\r\nconfirmation
    of induction of the seizure and microglia activity in the hippocampus as a focal
    point, we\r\ninvestigated whether these changes also reached the primary visual
    cortex (V1) as a secondary\r\ngeneralized seizure activity. Indeed, we found that
    microglia changed their morphology at high doses\r\nof KA in the V1. Next, we
    optimized each of the two methodological components: for the EEG recording,\r\nour
    initial attempts under the microscope suffered from extensive electrical noise,
    which overlaid the\r\nactual signal. Thus, we built a customized Faraday-cage
    and confirmed that the signal-to-noise ratio\r\nwas sufficiently reduced to be
    able to record brain oscillatory activity. For the in vivo live imaging of\r\nmicroglia,
    we had to optimize the imaging parameters, so that we would be able to detect
    microglial\r\nprocesses in a sufficient resolution to track their process changes.
    Finally, we combined both\r\nmethodologies with the KA model. We confirmed that
    KA induced seizure activity and found first\r\nindication that those correlate
    with microglia volume changes.\r\nOverall, we have developed a first methodological
    approach, which allows the analysis of the acute\r\neffects of seizure onset on
    microglia. Future studies will have to continue to optimize the drift during\r\nimaging
    recording and the post-image analysis. "
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: PreCl
alternative_title:
- ISTA Master's Thesis
article_processing_charge: No
author:
- first_name: Julie Stefanie
  full_name: Murmann, Julie Stefanie
  id: 1d390868-f128-11eb-9611-a0ca5f7833b5
  last_name: Murmann
citation:
  ama: 'Murmann JS. Investigating acute microglia response to seizure activity in
    vivo: Combining 2-Photon imaging and EEG recording. 2024. doi:<a href="https://doi.org/10.15479/at:ista:15352">10.15479/at:ista:15352</a>'
  apa: 'Murmann, J. S. (2024). <i>Investigating acute microglia response to seizure
    activity in vivo: Combining 2-Photon imaging and EEG recording</i>. Institute
    of Science and Technology Austria. <a href="https://doi.org/10.15479/at:ista:15352">https://doi.org/10.15479/at:ista:15352</a>'
  chicago: 'Murmann, Julie Stefanie. “Investigating Acute Microglia Response to Seizure
    Activity in Vivo: Combining 2-Photon Imaging and EEG Recording.” Institute of
    Science and Technology Austria, 2024. <a href="https://doi.org/10.15479/at:ista:15352">https://doi.org/10.15479/at:ista:15352</a>.'
  ieee: 'J. S. Murmann, “Investigating acute microglia response to seizure activity
    in vivo: Combining 2-Photon imaging and EEG recording,” Institute of Science and
    Technology Austria, 2024.'
  ista: 'Murmann JS. 2024. Investigating acute microglia response to seizure activity
    in vivo: Combining 2-Photon imaging and EEG recording. Institute of Science and
    Technology Austria.'
  mla: 'Murmann, Julie Stefanie. <i>Investigating Acute Microglia Response to Seizure
    Activity in Vivo: Combining 2-Photon Imaging and EEG Recording</i>. Institute
    of Science and Technology Austria, 2024, doi:<a href="https://doi.org/10.15479/at:ista:15352">10.15479/at:ista:15352</a>.'
  short: 'J.S. Murmann, Investigating Acute Microglia Response to Seizure Activity
    in Vivo: Combining 2-Photon Imaging and EEG Recording, Institute of Science and
    Technology Austria, 2024.'
corr_author: '1'
date_created: 2024-05-02T08:31:38Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-04-07T13:05:00Z
day: '02'
ddc:
- '570'
degree_awarded: MS
department:
- _id: SaSi
- _id: GradSch
doi: 10.15479/at:ista:15352
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  date_created: 2024-05-02T12:26:13Z
  date_updated: 2025-05-02T22:30:04Z
  embargo: 2025-05-02
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has_accepted_license: '1'
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '54'
publication_identifier:
  issn:
  - 2791-4585
publication_status: published
publisher: Institute of Science and Technology Austria
status: public
supervisor:
- first_name: Sandra
  full_name: Siegert, Sandra
  id: 36ACD32E-F248-11E8-B48F-1D18A9856A87
  last_name: Siegert
  orcid: 0000-0001-8635-0877
title: 'Investigating acute microglia response to seizure activity in vivo: Combining
  2-Photon imaging and EEG recording'
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  short: CC BY (4.0)
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2024'
...