Coordination of Escape and Spatial Navigation Circuits Orchestrate Versatile Flight from Threats

Abstract

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. We show activity in cholecystokinin-expressing hypothalamic dorsal premammillary cells (PMd-cck) is sufficient and necessary for context-specific escape that adapts to each environment’s layout. Contrastingly, numerous other nuclei implicated in flight only induced stereotyped panic-related escape. We reasoned the PMd is unique in its ability to induce context-specific escape because it projects to both escape and spatial navigation nuclei. Indeed, activity in PMd-cck projections to thalamic spatial navigation circuits are only 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 escapes. Thus, PMd-cck controls versatile flight engaging spatial navigation and escape circuits.