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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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Detalles Bibliográficos
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
Descripción
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.