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

Wang, W.; Schuette, P. J.; La-Vu, M. Q.; Tobias, B. C.; Ceko, M.; Kragel, P. A.; Reis, F. M.; Ji, S.; Sehgal, M.; Maesta-Pereira, S.; Chakerian, M.; Silva, A. J.; Canteras, N. S.; Wager, T.; Kao, J. C.; Adhikari, A.

doi:10.1101/2021.05.02.442354

bioRxiv · 10.1101/2021.05.02.442354

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

Wang, W.·Schuette, P. J.·La-Vu, M. Q.·Tobias, B. C.·Ceko, M.·Kragel, P. A.·Reis, F. M.·Ji, S.·Sehgal, M.·Maesta-Pereira, S.·Chakerian, M.·Silva, A. J.·Canteras, N. S.·Wager, T.·Kao, J. C.·Adhikari, A.

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Abstract

Escape from threats has paramount importance for survival. However, it is unknown if a single circuit controls escape from innate and conditioned threats. The hypothalamic dorsal premammillary nucleus (PMd) may control escape, as it is activated by escape-inducing threats and projects to the region most implicated in flight, the dorsolateral periaqueductal gray (dlPAG). We show that in mice cholecystokinin (cck)-expressing PMd 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. Lastly, human fMRI 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 as a central node of the escape network.

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Wang, W., Schuette, P. J., La-Vu, M. Q., Tobias, B. C., Ceko, M., Kragel, P. A., Reis, F. M., Ji, S., Sehgal, M., Maesta-Pereira, S., Chakerian, M., Silva, A. J., Canteras, N. S., Wager, T., Kao, J. C., Adhikari, A.. 2021-05-02. Dorsal premammillary projection to periaqueductal gray controls escape vigor from innate and conditioned threats. https://doi.org/10.1101/2021.05.02.442354

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