Zona Incerta Suppressed Escape During Hunger

Wild animals must avoid starvation and predators to survive. However, the motivation to seek food and shelter promote opposing behaviors and require rapid neural adaptations that are poorly understood. The zona incerta (ZI) is a specialized region that integrates multisensory input, projects strongly to motor-related regions, and can thus initiate escape from threats to survive. One subset of medial ZI neurons producing dopamine (DA) and gamma-aminobutyric acid (GABA) send dense projections to the medial motor-related superior colliculus (SCm), which promotes escape from threats in the upper visual field. We determined whether ZI-GABA/DA cells respond to hunger and investigated whether activating ZI-GABA/DA cells in hungry mice suppressed escape. We transduced ZI-GABA/DA cells with an excitatory chemogenetic receptor hM3(Dq) and found that stimulating their projections in the medial SCm suppressed escape from an upper visual threat in male and female mice. Interestingly, fasting activated ZI-GABA/DA cells and enhanced hM3(Dq)-mediated escape suppression. To evaluate the contribution of GABA and/or DA in escape suppression, we co-infused a cocktail of DA or GABA receptor antagonists, respectively. Both GABA and DA are required to suppress escape in fasted male mice, but DA independently suppressed escape in female mice. Activation of ZI-GABA/DA cells did not impact locomotor or any anxiety-related functions but uniquely integrated hunger signals to suppress escape. Our findings suggested that the ZI-SCm neurocircuit is sexually dimorphic and that the ZI is a critical node regulating the competition between the need to seek food and shelter.