Coordination of escape and spatial navigation circuits orchestrates versatile flight from threats

• DOI: 10.1016/j.neuron.2021.03.033
• Publication Date: 2021-04-16T07:31:11Z
• Authors: Weisheng Wang; Peter J. Schuette; Jun Nagai; Brooke Christine ...; Fernando Midea Cu...; Shiyu Ji; Miguel A.X. de Lima; Mimi Q. La-Vu; Sandra Maesta-Per...; Meghmik Chakerian; Saskia J. Leonard; Lilly Lin; Amie L. Severino; Catherine M. Cahill; Newton S. Canteras; Baljit S. Khakh; Jonathan C. Kao; Avishek Adhikari
• Keywords: Escape response; Periaqueductal gray; Spatial contextual awareness

Naturalistic escape requires versatile context-specific flight with rapid evaluation of local geometry to identify and use efficient escape routes. It is unknown how spatial navigation and escape circuits are recruited to produce context-specific flight. Using mice, we show that activity in cholecystokinin-expressing hypothalamic dorsal premammillary nucleus (PMd-cck) cells is sufficient and necessary for context-specific escape that adapts to each environment's layout. In contrast, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the dorsal premammillary nucleus (PMd) can induce context-specific escape because it projects to escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits is necessary for context-specific escape induced by moderate threats but not panic-related stereotyped escape caused by perceived asphyxiation. Conversely, the PMd projection to the escape-inducing dorsal periaqueductal gray projection is necessary for all tested escapes. Thus, PMd-cck cells control versatile flight, engaging spatial navigation and escape circuits.