Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
- University of California, Los Angeles, United States
- University of Colorado, United States
- UCLA, United States
- University of São Paulo, Brazil
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
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Data from: Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threatsDryad Digital Repository, doi:10.5068/dryad.D19H5X.
Article and author information
Author details
Sandra Maesta-Pereira
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.
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.
Reviewing Editor
- Justin Moscarello
Publication history
- Received: April 7, 2021
- Preprint posted: May 2, 2021 (view preprint)
- Accepted: August 28, 2021
- Accepted Manuscript published: September 1, 2021 (version 1)
- 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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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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