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

Neuron. 2021 Jun 2;109(11):1848-1860.e8. doi: 10.1016/j.neuron.2021.03.033. Epub 2021 Apr 15.


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.

Keywords: Dorsal premammillary nucleus; Dorsolateral periaqueductal gray; Escape; Fear; Panic; Predator; anterior medial ventral thalamus; calcium imaging; hypercapnia; optogenetics.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Escape Reaction*
  • Female
  • Hypothalamus, Posterior / physiology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neural Pathways / physiology
  • Periaqueductal Gray / physiology*
  • Rats
  • Rats, Long-Evans
  • Spatial Navigation*
  • Thalamus / physiology*