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Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
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Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
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Journal Article
Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats
2021
Overview
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.
Publisher
eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
Subject
/ Animals
/ Behavior
/ Cholecystokinin - metabolism
/ dorsal premammillary nucleus
/ escape
/ Fear
/ Female
/ Functional magnetic resonance imaging
/ Humans
/ Hypothalamus, Posterior - diagnostic imaging
/ Hypothalamus, Posterior - metabolism
/ Hypothalamus, Posterior - physiology
/ Male
/ Males
/ Mice
/ Neural Pathways - physiology
/ panic
/ Periaqueductal Gray - diagnostic imaging
/ Periaqueductal Gray - metabolism
/ Periaqueductal Gray - physiology
/ predator
/ Rats
/ Threats
/ Velocity
/ Vigor
