Toggling between food-seeking and self-preservation behaviors via hypothalamic response networks

Neuron. 2023 Sep 20;111(18):2899-2917.e6. doi: 10.1016/j.neuron.2023.06.006. Epub 2023 Jul 12.

Abstract

Motivated behaviors are often studied in isolation to assess labeled lines of neural connections underlying innate actions. However, in nature, multiple systems compete for expression of goal-directed behaviors via complex neural networks. Here, we examined flexible survival decisions in animals tasked with food seeking under predation threat. We found that predator exposure rapidly induced physiological, neuronal, and behavioral adaptations in mice highlighted by reduced food seeking and consumption contingent on current threat level. Diminishing conflict via internal state or external environment perturbations shifted feeding strategies. Predator introduction and/or selective manipulation of danger-responsive cholecystokinin (Cck) cells of the dorsal premammilary nucleus (PMd) suppressed hunger-sensitive Agouti-related peptide (AgRP) neurons, providing a mechanism for threat-evoked hypophagia. Increased caloric need enhanced food seeking under duress through AgRP pathways to the bed nucleus of the stria terminalis (BNST) and/or lateral hypothalamus (LH). Our results suggest oscillating interactions between systems underlying self-preservation and food seeking to promote optimal behavior.

Keywords: calcium imaging; cell-specific perturbation; chemogenetics; choice; conflict behavior; feeding; foraging; in vivo neural activity recordings; optogenetics; self-preservation.

Publication types

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

MeSH terms

  • Agouti-Related Protein / metabolism
  • Animals
  • Hunger / physiology
  • Hypothalamic Area, Lateral / physiology
  • Hypothalamus* / metabolism
  • Mice
  • Neurons* / physiology

Substances

  • Agouti-Related Protein