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

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Wang, Weisheng ^[1] ; Schuette, Peter J. ^[1] ; La-Vu, Mimi Q. ^[1] ; Torossian, Anita ^[2] ; Tobias, Brooke C. ^[1] ; Ceko, Marta ^[3] ; Kragel, Philip A. ^[4] ; Reis, V, Fernando M. C. ; Ji, Shiyu ^[5] ; Sehgal, Megha ^[6] ; Maesta-Pereira, Sandra ^[2] ; Chakerian, Meghmik ^[5] ; Silva, Alcino J. ^{[7, 5, 6]} ; Canteras, Newton S. ^[8] ; Wager, Tor ^[4] ; Kao, Jonathan C. ^[9] ; Adhikari, Avishek ^[5]

Afiliação do(s) autor(es)

^[1] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 - USA

^[2] Univ Calif Los Angeles, Los Angeles, CA - USA

^[3] Univ Colorado, Inst Cognit Sci, Boulder, CO 80309 - USA

^[4] Univ Colorado, Boulder, CO 80309 - USA

^[5] Reis, Fernando M. C., V, Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 - USA

^[6] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA - USA

^[7] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 - USA

^[8] Univ Sao Paulo, Dept Anat, Sao Paulo - Brazil

^[9] Univ Calif Los Angeles, Elect & Comp Engn, Los Angeles, CA - USA

• Tipo de documento: Artigo Científico
• Fonte: eLIFE; v. 10, SEP 1 2021.
• Citações Web of Science: 0

Resumo

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. (AU)

• Processo FAPESP: 17/08668-1 - Estudo in vivo de populações neuronais GABAérgicas e glutamatérgicas da substância cinzenta periaquedutal em resposta a diferentes tipos de ameaça
• Beneficiário: Fernando Midea Cuccovia Vasconcelos Reis
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Pós-Doutorado
• Processo FAPESP: 15/23092-3 - Investigação das vias de sinalização envolvidas na formação da memória de medo em animais expostos ao predador
• Beneficiário: Fernando Midea Cuccovia Vasconcelos Reis
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 14/05432-9 - Bases neurais do medo e agressão
• Beneficiário: Newton Sabino Canteras
• Modalidade de apoio: Auxílio à Pesquisa - Temático