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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eLife Sciences Publications Ltd
2021
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oai:doaj.org-article:7333c19037ed4e3bbeb22847fc8ed52e2021-11-26T11:12:28ZDorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats10.7554/eLife.691782050-084Xe69178https://doaj.org/article/7333c19037ed4e3bbeb22847fc8ed52e2021-09-01T00:00:00Zhttps://elifesciences.org/articles/69178https://doaj.org/toc/2050-084XEscape 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.Weisheng WangPeter J SchuetteMimi Q La-VuAnita TorossianBrooke C TobiasMarta CekoPhilip A KragelFernando MCV ReisShiyu JiMegha SehgalSandra Maesta-PereiraMeghmik ChakerianAlcino J SilvaNewton S CanterasTor WagerJonathan C KaoAvishek AdhikarieLife Sciences Publications Ltdarticleperiaqueductal graydorsal premammillary nucleuspredatorpanicfearescapeMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021) |
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periaqueductal gray dorsal premammillary nucleus predator panic fear escape Medicine R Science Q Biology (General) QH301-705.5 |
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periaqueductal gray dorsal premammillary nucleus predator panic fear escape Medicine R Science Q Biology (General) QH301-705.5 Weisheng Wang Peter J Schuette Mimi Q La-Vu Anita Torossian Brooke C Tobias Marta Ceko Philip A Kragel Fernando MCV Reis Shiyu Ji Megha Sehgal Sandra Maesta-Pereira Meghmik Chakerian Alcino J Silva Newton S Canteras Tor Wager Jonathan C Kao Avishek Adhikari Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats |
| 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. |
| format |
article |
| author |
Weisheng Wang Peter J Schuette Mimi Q La-Vu Anita Torossian Brooke C Tobias Marta Ceko Philip A Kragel Fernando MCV Reis Shiyu Ji Megha Sehgal Sandra Maesta-Pereira Meghmik Chakerian Alcino J Silva Newton S Canteras Tor Wager Jonathan C Kao Avishek Adhikari |
| author_facet |
Weisheng Wang Peter J Schuette Mimi Q La-Vu Anita Torossian Brooke C Tobias Marta Ceko Philip A Kragel Fernando MCV Reis Shiyu Ji Megha Sehgal Sandra Maesta-Pereira Meghmik Chakerian Alcino J Silva Newton S Canteras Tor Wager Jonathan C Kao Avishek Adhikari |
| author_sort |
Weisheng Wang |
| title |
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_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_sort |
dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats |
| publisher |
eLife Sciences Publications Ltd |
| publishDate |
2021 |
| url |
https://doaj.org/article/7333c19037ed4e3bbeb22847fc8ed52e |
| work_keys_str_mv |
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