A midbrain-to-ventral-striatum dopaminergic pathway orchestrates odor-guided insect predation in mice

Foraging and food consumption are fundamental for the survival of animals. In natural environments, wild rodents feed on insects, including moth larvae, and odor-guided evaluation of potential food resources is a critical step in initiating feeding behavior. However, the mechanisms by which rodents seek and feed on insect prey remain poorly understood. Herein, we employed a laboratory-based predator–prey interaction system using mice and cotton bollworm larvae to investigate the neural mechanisms underlying food-seeking and feeding behaviors at both cellular and neural circuit levels. We demonstrate that mice exhibit a strong preference for consuming fed larvae, and this preference is dependent on the main olfactory system. Gas chromatography-mass spectrometry analysis revealed significant differences in the chemical profiles of fed and unfed larvae, with fed larvae containing a higher level of linoleic acid (LA) and a lower level of (Z)-9-tricosene [(Z)-9-TE]. Behavioral assays showed that mice, as well as Brand’s voles and brown rats, are attracted to LA but avoid (Z)-9-TE in a two-choice odor preference test. Furthermore, we identified that the dopaminergic pathway from the ventral tegmental area (VTA) to the medial olfactory tubercle (mOT) plays a central role in mediating this preference. Chemogenetic inhibition of this pathway abolished the preference for LA over (Z)-9-TE, while chemogenetic activation reversed this effect. Additionally, fiber photometry recordings and pharmacology revealed that mOT D1 and D2 spiny projection neurons preferentially mediate attraction to LA and avoidance of (Z)-9-TE, respectively. These findings uncover a neurobiological system in rodents that supports insect predation based upon chemosignals.