Hunger enhances food odor attraction through a Neuropeptide Y spotlight

Internal state controls olfaction through poorly understood mechanisms. Odors signifying food, mates, competitors, and predators activate parallel neural circuits that may be flexibly shaped by physiological need to alter behavioral outcome(1). Here, we identify a neuronal mechanism by which hunger selectively promotes attraction to food odors over other olfactory cues. Optogenetic activation of hypothalamic Agouti-Related Peptide (AGRP) neurons enhances attraction to food odors but not pheromones, with branch-specific activation and inhibition revealing a key role for projections to the paraventricular thalamus. Knockout mice lacking Neuropeptide Y (NPY) or NPY receptor type 5 (NPY5R) fail to prefer food odors over pheromones after fasting, with hunger-dependent food odor attraction restored by cell-specific NPY rescue in AGRP neurons. Furthermore, acute NPY injection immediately rescues behavior without additional training, indicating that NPY is required for reading olfactory circuits during behavioral expression rather than writing olfactory circuits during odor learning. Together, these findings show that food odor-responsive neurons comprise an olfactory subcircuit that listens to hunger state through thalamic NPY release, and more generally, provide mechanistic insights into how internal state regulates behavior.