# MECHANISMS UNDERLYING OLFACTORY EFFECTS ON APPETITE

> **NIH NIH R01** · FRED HUTCHINSON CANCER RESEARCH CENTER · 2020 · $680,215

## Abstract

Appetite is a basic drive that is essential to survival. The olfactory system can have potent effects on appetite
in mammals, with certain odors stimulating appetite in humans, and either increasing or decreasing food intake
and body weight in rodents. In the mouse, as in other mammals, olfactory sensory signals travel from olfactory
sensory neurons in the nasal olfactory epithelium through the olfactory bulb to the olfactory cortex and then to
other brain areas. Odorants are detected in the nose by ~1000 different odorant receptors (ORs), each
expressed by a different subset of sensory neurons. Neurons with the same OR are scattered in one nasal
spatial zone, but their axons converge in a few specific glomeruli in the olfactory bulb, creating a semi-
stereotyped sensory map in which each glomerulus and its associated mitral and tufted relay neurons, which
project to the cortex, appears dedicated to one OR. Signals from each glomerulus travel to multiple distinct
areas of the olfactory cortex. How the vast array of sensory information generated by this organization might
impact appetite is unexplored. To begin to investigate this question, we conducted preliminary studies on
olfactory inputs to two subsets of neurons linked to appetite, both of which are located in the arcuate nucleus of
the hypothalamus: AGRP (agouti related peptide) neurons, which can enhance appetite, and POMC (pro-
opiomelanocortin) neurons, which can suppress appetite. We found that only some odors affect the activity of
AGRP or POMC neurons and that different odors activate AGRP versus POMC neurons. Using a
Pseudorabies virus (PRV) that travels retrogradely across multiple synapses, we found evidence for neurons
upstream of AGRP and POMC neurons in the olfactory cortex, but only in certain olfactory cortical areas.
These observations are consistent with the idea that some olfactory sensory inputs can have innate effects on
appetite and that those effects involve genetically programmed neural circuits that convey signals from specific
ORs in the nose through the olfactory system to hypothalamic neurons that regulate appetite. In the studies
proposed in this application, we will test the hypotheses that 1) AGRP and POMC neurons can receive input
from selected ORs that are similar among individuals and recognize odorants that affect the activity of the
appetite neurons and appetite behaviors, 2) neurons within specific areas of the olfactory cortex can influence
AGRP or POMC neuron activity and appetite-associated behaviors, and 3) odor-responsive neurons in other
brain areas can relay signals from the olfactory cortex to AGRP or POMC neurons to modulate their activity
and regulate behaviors associated with appetite. Together, these studies should provide significant new
insights into the molecular mechanisms and neural circuits that govern the impact of olfactory sensory signals
on appetite.

## Key facts

- **NIH application ID:** 9872142
- **Project number:** 5R01DC016941-03
- **Recipient organization:** FRED HUTCHINSON CANCER RESEARCH CENTER
- **Principal Investigator:** Linda B Buck
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $680,215
- **Award type:** 5
- **Project period:** 2018-03-15 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872142

## Citation

> US National Institutes of Health, RePORTER application 9872142, MECHANISMS UNDERLYING OLFACTORY EFFECTS ON APPETITE (5R01DC016941-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9872142. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*