Summary: A study of hungry mice reveals new insights into the neurobiology of smell and food-seeking behavior. Researchers have mapped a neural pathway that biases attraction toward food odors over other olfactory signals.
Source: Harvard
Animals rely on smell to find food, detect mates and sense danger. When an animal encounters both food and a potential mate at once, how does it prioritize eating over mating? What makes food odors more compelling when an animal is hungry?
Work from Harvard Medical School investigators sheds light on how internal hunger signals steer attention toward food-related smells. The research identifies a brain circuit and chemical messenger that increase the attractiveness of food odors when an animal is in a hungry state.
Published March 3 in Nature, the study by Stephen Liberles and co-author Nao Horio pinpointed a signaling molecule—neuropeptide Y (NPY)—and its receptor NPY5R as central drivers of hunger-dependent odor preference.
The team focused on how specific neurons convey hunger state to olfactory circuits through the thalamus, a brain region that relays sensory information to the cortex and participates in many physiological processes.
“We found that particular neurons register hunger by releasing the neurotransmitter NPY in the thalamus,” said Liberles, professor of cell biology at the Blavatnik Institute and an investigator at the Howard Hughes Medical Institute.
Choosing between food and mating cues
“In mice, food odors and sex pheromones are both attractive, but they serve different physiological needs,” said Horio, a postdoctoral researcher in the Liberles lab. “This implies that distinct olfactory circuits can be selectively prioritized depending on internal state.”
To explore how mice select between competing odors, Horio designed a behavioral test with two scent ports: one releasing the smell of standard mouse chow and the other presenting pheromones from an opposite-sex animal. The researchers measured the time each mouse spent investigating each port as an index of preference.
When mice were well fed, they showed roughly equal interest in food odors and pheromones. After fasting, however, mice exhibited a clear shift: hungry animals spent much more time investigating food odors than pheromones. Fed mice that had prior exposure to a potential mate preferred pheromones, while hungry mice did not—indicating hunger can override mating-related attraction.
Tracing the chemical signals of hunger
The researchers examined neurons in the hypothalamus known to drive feeding behavior. These neurons release agouti-related peptide (AGRP) and other transmitters that promote food-seeking.
Using optogenetics—a method that activates neurons with light—the team showed that stimulating AGRP neurons made even sated mice behave like they were hungry, increasing investigation of food odors.
AGRP neurons project to many targets across the brain. By selectively activating and inhibiting branches of these neurons, the authors identified projections to the paraventricular thalamus as critical for changing odor preference. Activating AGRP terminals in this thalamic region made non-hungry mice prefer food scents; silencing them reduced food-odor attraction in hungry mice.
“Persistent AGRP activity during fasting appears to enhance food-odor attraction by continuously signaling to downstream neurons,” Liberles explained.
Next, the team tested which neurotransmitters released by AGRP neurons were necessary for hunger-dependent odor preference. AGRP neurons release three principal signals: AGRP itself, NPY, and GABA. The researchers used genetically modified mice lacking each of these transmitters in turn.
Mice lacking AGRP or GABA still showed increased attraction to food odors when hungry. By contrast, animals missing NPY failed to prefer food odors over pheromones after fasting. NPY knockout mice, whether fed or fasted, displayed similar, lower levels of attraction to food odors comparable to their interest in pheromones. Likewise, mice lacking the NPY receptor NPY5R lost hunger-dependent preference for food odor.
Additionally, after social exposure to a potential mate, mice without NPY were more drawn to pheromones than to food, suggesting that distinct mechanisms enhance responses to mating cues independently of NPY.
The findings indicate that hunger triggers a signaling cascade in which thalamic NPY release acts as a spotlight, selectively enhancing activity in food-odor-responsive olfactory circuits. Cell-specific restoration of NPY in AGRP neurons rescued the fasting-induced food-odor preference, and acute NPY administration rapidly reinstated food-odor attraction without requiring new odor learning.
“It appears different neurotransmitters may act as spotlights for other behavioral drives, with the thalamus functioning as a switchboard that prioritizes sensory inputs based on physiological need,” Liberles said.
Funding: The study was supported by the National Institutes of Health (R01 DC013289), the Uehara Memorial Foundation, the Mishima Kaiun Memorial Foundation, and the Howard Hughes Medical Institute.
About this olfaction research news
Source: Harvard
Contact: Ekaterina Pesheva – Harvard
Image: The image is in the public domain
Original Research: Closed access. “Hunger enhances food-odour attraction through a neuropeptide Y spotlight” by Nao Horio & Stephen D. Liberles. Nature
Abstract
Hunger enhances food-odour attraction through a neuropeptide Y spotlight
Internal state shapes olfactory behavior through mechanisms that are not fully understood. Odors representing food, mates, competitors and predators activate parallel neural pathways that can be flexibly modulated by physiological need. This study identifies a neuronal mechanism by which hunger selectively enhances attraction to food odors over other olfactory cues.
Optogenetic activation of hypothalamic AGRP neurons selectively increases attraction to food odors, while branch-specific manipulations highlight projections to the paraventricular thalamus as key. Mice lacking NPY or the NPY receptor NPY5R do not prefer food odors to pheromones after fasting, and restoring NPY specifically in AGRP neurons rescues hunger-dependent odor preference.
Acute NPY administration rapidly restores food-odor preference without additional learning, indicating NPY is required for the real-time reading of olfactory circuits during behavioral expression rather than for forming odor associations. Overall, these results reveal an olfactory subcircuit that listens to hunger state through thalamic NPY release and provide broader insight into how internal physiological states regulate behavior.