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

eLife

Newton S Canteras¹  Megha Sehgal²  Peter J Schuette³  Mimi Q La-Vu³  Fernando MCV Reis³  Weisheng Wang³  Meghmik Chakerian³  Avishek Adhikari³  Brooke C Tobias³  Shiyu Ji³  Alcino J Silva⁴  Jonathan C Kao⁵  Marta Ceko⁶  Sandra Maesta-Pereira⁷  Anita Torossian⁷  Philip A Kragel⁸  Tor Wager⁸ 

[1] Department of Anatomy, University of São Paulo, Sao Paulo, Brazil;Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States;Department of Psychology, University of California, Los Angeles, Los Angeles, United States;Department of Psychology, University of California, Los Angeles, Los Angeles, United States;Department of Neurobiology, University of California, Los Angeles, Los Angeles, United States;Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, United States;Electrical and Computer Engineering, University of California, Los Angeles, Los Angeles, United States;Institute of Cognitive Science, University of Colorado, Boulder, United States;University of California, Los Angeles, Los Angeles, United States;University of Colorado, Boulder, United States;

关键词: periaqueductal gray;    dorsal premammillary nucleus;    predator;    panic;    fear;    escape;    Mouse;   

DOI  :  10.7554/eLife.69178

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY