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

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 inna...

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Autores principales: Wang, Weisheng, Schuette, Peter J, La-Vu, Mimi Q, Torossian, Anita, Tobias, Brooke C, Ceko, Marta, Kragel, Philip A, Reis, Fernando MCV, Ji, Shiyu, Sehgal, Megha, Maesta-Pereira, Sandra, Chakerian, Meghmik, Silva, Alcino J, Canteras, Newton S, Wager, Tor, Kao, Jonathan C, Adhikari, Avishek
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457830/
https://www.ncbi.nlm.nih.gov/pubmed/34468312
http://dx.doi.org/10.7554/eLife.69178
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author Wang, Weisheng
Schuette, Peter J
La-Vu, Mimi Q
Torossian, Anita
Tobias, Brooke C
Ceko, Marta
Kragel, Philip A
Reis, Fernando MCV
Ji, Shiyu
Sehgal, Megha
Maesta-Pereira, Sandra
Chakerian, Meghmik
Silva, Alcino J
Canteras, Newton S
Wager, Tor
Kao, Jonathan C
Adhikari, Avishek
author_facet Wang, Weisheng
Schuette, Peter J
La-Vu, Mimi Q
Torossian, Anita
Tobias, Brooke C
Ceko, Marta
Kragel, Philip A
Reis, Fernando MCV
Ji, Shiyu
Sehgal, Megha
Maesta-Pereira, Sandra
Chakerian, Meghmik
Silva, Alcino J
Canteras, Newton S
Wager, Tor
Kao, Jonathan C
Adhikari, Avishek
author_sort Wang, Weisheng
collection PubMed
description 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 functional magnetic resonance imaging 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.
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spelling pubmed-84578302021-09-24 Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats Wang, Weisheng Schuette, Peter J La-Vu, Mimi Q Torossian, Anita Tobias, Brooke C Ceko, Marta Kragel, Philip A Reis, Fernando MCV Ji, Shiyu Sehgal, Megha Maesta-Pereira, Sandra Chakerian, Meghmik Silva, Alcino J Canteras, Newton S Wager, Tor Kao, Jonathan C Adhikari, Avishek eLife Neuroscience 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 functional magnetic resonance imaging 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. eLife Sciences Publications, Ltd 2021-09-01 /pmc/articles/PMC8457830/ /pubmed/34468312 http://dx.doi.org/10.7554/eLife.69178 Text en © 2021, Wang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Wang, Weisheng
Schuette, Peter J
La-Vu, Mimi Q
Torossian, Anita
Tobias, Brooke C
Ceko, Marta
Kragel, Philip A
Reis, Fernando MCV
Ji, Shiyu
Sehgal, Megha
Maesta-Pereira, Sandra
Chakerian, Meghmik
Silva, Alcino J
Canteras, Newton S
Wager, Tor
Kao, Jonathan C
Adhikari, Avishek
Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
title Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
title_full Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
title_fullStr Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
title_full_unstemmed Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
title_short Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
title_sort dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8457830/
https://www.ncbi.nlm.nih.gov/pubmed/34468312
http://dx.doi.org/10.7554/eLife.69178
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