1. Neuroscience

Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats

  1. Weisheng Wang
  2. Peter J Schuette
  3. Mimi Q La-Vu
  4. Anita Torossian
  5. Brooke C Tobias
  6. Marta Ceko
  7. Philip A Kragel
  8. Fernando MCV Reis
  9. Shiyu Ji
  10. Megha Sehgal
  11. Sandra Maesta-Pereira
  12. Meghmik Chakerian
  13. Alcino J Silva
  14. Newton S Canteras
  15. Tor Wager
  16. Jonathan C Kao
  17. Avishek Adhikari  Is a corresponding author
  1. University of California, Los Angeles, United States
  2. University of Colorado, United States
  3. UCLA, United States
  4. University of São Paulo, Brazil
https://doi.org/10.7554/eLife.69178
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Cite this article
  1. Weisheng Wang
  2. Peter J Schuette
  3. Mimi Q La-Vu
  4. Anita Torossian
  5. Brooke C Tobias
  6. Marta Ceko
  7. Philip A Kragel
  8. Fernando MCV Reis
  9. Shiyu Ji
  10. Megha Sehgal
  11. Sandra Maesta-Pereira
  12. Meghmik Chakerian
  13. Alcino J Silva
  14. Newton S Canteras
  15. Tor Wager
  16. Jonathan C Kao
  17. Avishek Adhikari
(2021)
Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
eLife 10:e69178.
https://doi.org/10.7554/eLife.69178
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  3. Download .RIS

Abstract

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape vigor from innate and conditioned threats. Cholecystokinin (cck)-expressing cells in the hypothalamic dorsal premammillary nucleus (PMd) are necessary for initiating escape from innate threats via a projection to the dorsolateral periaqueductal gray (dlPAG). We now show that in mice PMd-cck cells are activated during escape, but not other defensive behaviors. PMd-cck ensemble activity can also predict future escape. Furthermore, PMd inhibition decreases escape speed from both innate and conditioned threats. Inhibition of the PMd-cck projection to the dlPAG also decreased escape speed. Intriguingly, PMd-cck and dlPAG activity in mice showed higher mutual information during exposure to innate and conditioned threats. In parallel, human fMRI data show that a posterior hypothalamic-to-dlPAG pathway increased activity during exposure to aversive images, indicating that a similar pathway may possibly have a related role in humans. Our data identify the PMd-dlPAG circuit as a central node, controlling escape vigor elicited by both innate and conditioned threats.

Data availability

All custom written software has been uploaded to https://github.com/schuettepeter/PMd_escape_vigorData has been uploaded tohttps://datadryad.org/stash/dataset/doi:10.5068/D19H5X

The following data sets were generated

Article and author information

Author details

  1. Weisheng Wang

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Peter J Schuette

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Mimi Q La-Vu

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Anita Torossian

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Brooke C Tobias

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2043-9523

  6. Marta Ceko

    Institute of Cognitive Science, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Philip A Kragel

    Institute of Cognitive Science, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Fernando MCV Reis

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0121-2887

  9. Shiyu Ji

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3413-5766

  10. Megha Sehgal

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  11. Sandra Maesta-Pereira

    Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6522-8311

  12. Meghmik Chakerian

    Psychology, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.

  13. Alcino J Silva

    Departments of Neurobiology, Psychiatry & Biobehavioral Sciences, and Psychology, UCLA, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1587-4558

  14. Newton S Canteras

    Department of Anatomy, University of São Paulo, Sao Paulo, Brazil
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7205-5372

  15. Tor Wager

    Institute of Cognitive Science, University of Colorado, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  16. Jonathan C Kao

    Electrical and Computer Engineering, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9298-0143

  17. Avishek Adhikari

    Psychology, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    avi@psych.ucla.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9187-9211

Funding

National Institutes of Health (R00 MH106649)

  • Avishek Adhikari

Fundação de Amparo à Pesquisa do Estado de São Paulo (2017/08668-1)

  • Fernando MCV Reis

Fundação de Amparo à Pesquisa do Estado de São Paulo (2014/05432-9)

  • Newton S Canteras

Hellman Foundation

  • Avishek Adhikari

Achievement Rewards for College Scientists Foundation

  • Mimi Q La-Vu

National Institutes of Health (R01 MH119089)

  • Avishek Adhikari

Brain and Behavior Research Foundation (22663)

  • Avishek Adhikari

Brain and Behavior Research Foundation (27654)

  • Fernando MCV Reis

Brain and Behavior Research Foundation (27780)

  • Weisheng Wang

Brain and Behavior Research Foundation (29204)

  • Jonathan C Kao

National Institutes of Health (F31 MH121050-01A1)

  • Mimi Q La-Vu

National Science Foundation (DGE-1650604)

  • Peter J Schuette

Fundação de Amparo à Pesquisa do Estado de São Paulo (2015/23092-3)

  • Fernando MCV Reis

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Justin Moscarello

Ethics

Animal experimentation: All procedures have been approved by the University of California, Los Angeles Institutional Animal Care and Use Committee, protocols 2017-011 and 2017-075.

Version history

  1. Received: April 7, 2021
  2. Preprint posted: May 2, 2021 (view preprint)
  3. Accepted: August 28, 2021
  4. Accepted Manuscript published: September 1, 2021 (version 1)
  5. Version of Record published: September 22, 2021 (version 2)

Copyright

© 2021, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Weisheng Wang
  2. Peter J Schuette
  3. Mimi Q La-Vu
  4. Anita Torossian
  5. Brooke C Tobias
  6. Marta Ceko
  7. Philip A Kragel
  8. Fernando MCV Reis
  9. Shiyu Ji
  10. Megha Sehgal
  11. Sandra Maesta-Pereira
  12. Meghmik Chakerian
  13. Alcino J Silva
  14. Newton S Canteras
  15. Tor Wager
  16. Jonathan C Kao
  17. Avishek Adhikari
(2021)
Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
eLife 10:e69178.
https://doi.org/10.7554/eLife.69178

Share this article

https://doi.org/10.7554/eLife.69178

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