What are the neural and behavioral mechanisms that enable mice to identify, navigate toward, and initiate consumption of a food source? A research group led by Professor ZHANG Yun-Feng from the Institute of Zoology at the Chinese Academy of Sciences, published in the Proceedings of the National Academy of Sciences (PNAS), deciphered the neural encoding mechanism that are responsible for mice utilizing their olfactory system to assess the nutritional state of prey and execute precise foraging decisions at the molecular, cellular, and neural circuit levels.

In natural environments, animals often rely on odors to evaluate the nutritional value of food. Odor molecules from food sources provide predators with crucial information regarding nutritional quality and palatability. The ability of mice to assess the nutritional status of food resources via olfactory cues likely determines whether they initiate feeding behavior or not; however, the underlying neural mechanism remains unclear.

The researchers established a behavioral experimental system mimicking natural predation, using cotton bollworm larvae as the prey of the predator—mice. Intriguingly, regardless of whether mice were in a fasted or sated state, they all showed a significant preference for fed larvae over unfed ones. The main olfactory system is indispensable during this process. Using gas chromatography–mass spectrometry, the researchers precisely identified two key chemical compounds from larval body surface volatiles: linoleic acid (LA), which was present at higher levels on well-fed larvae, and (Z)-9-tricosene [(Z)-9-TE], which was significantly enriched on the body surface of unfed larvae.

Further investigation revealed that LA attracted mice, whereas (Z)-9-TE elicited avoidance behavior, with both exhibiting dose-dependent response. Additional studies identified the dopaminergic neural pathway originating from the ventral tegmental area (VTA) and projecting to the medial olfactory tubercle (mOT) as a crucial hub in regulating the odor preference.

In vivo fiber photometry and pharmacological experiments revealed that D1- and D2-type medium spiny projection neurons in the mOT responded specifically to LA and (Z)-9-TE, respectively. Specifically, D1 receptor signaling mediated attraction toward LA, while D2 receptor signaling was involved in avoidance of (Z)-9-TE. These two signaling pathways form an exquisitely balanced "seesaw"-like working model to orchestrate larvae predation in mice.

This work advances our understanding of ecological species interactions and holds potential for developing pest management strategies by targeting conserved olfactory evaluation pathways.

Schematic demonstrating a “seesaw” working model of the VTA-mOT dopaminergic pathway in orchestrating preference for fed over unfed larvae.

 (Image by ZHANG Yun-Feng's group)