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: 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
Formato: article
Lenguaje:EN
Publicado: eLife Sciences Publications Ltd 2021
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Acceso en línea:https://doaj.org/article/7333c19037ed4e3bbeb22847fc8ed52e
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Sumario: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.