# Olfactory neuromodulation: genes, cells, and behavior

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2024 · $504,644

## Abstract

PROJECT SUMMARY
Day/night cycles profoundly impact animals’ physiology and behavior to allow adaptation to rhythmic environmental
cues. Daily rhythmic behaviors are believed to be patterned by central clock neurons. However, the physiology of
primary sensory neurons, such as olfactory receptor neurons (ORNs), can also exhibit oscillatory changes, but
whether such changes can guide rhythmic behaviors remains undetermined. Progress is further hindered by the lack
of information on whether or which odor-guided behaviors are regulated by day/night cycles. This proposal leverages
the powerful genetic toolkit and tractable olfactory system of D. melanogaster to address these fundamental yet
outstanding questions. Preliminary studies showed that pheromone-sensing ORNs exhibit higher responses in flies
at subjective night (henceforth referred to as night flies) than in flies at subjective day (henceforth referred to as day
flies). Importantly, this heightened pheromone sensitivity in night flies in turn elevates odor-guided social behavior.
Mechanistically, the day or night modulation is respectively signaled via two neuromodulators. Preliminary
experiments further showed that in theses ORNs, the day/night modulation of olfactory acuity requires a cation
channel subunit whose expression likely reduces neuronal input resistance or causes accommodation, thus lowering
spike response frequency. These findings led to the hypothesis that day/night cycles, through the antagonistic actions
of two neuromodulators, up- or down-regulate the cation channel in ORNs to dynamically modulate olfactory acuity
and odor-guided behavior. To test this central hypothesis, this research will determine how the two neuromodulators
antagonistically regulate ORN responses (Aim 1), characterize the effector(s) capable of altering olfactory responses
in the target ORNs (Aim 2), and investigate the generality of the neuromodulatory mechanism across ORN types
(Aim 3). The mechanistic insights expected from this research will advance our understanding of how day/night cycles
influence olfactory physiology and behavior. Of further significance, this research demonstrates that neuromodulatory
impairment at the ORN level precludes the potential influence of central circadian mechanisms on odor-guided
behavior. The idea that peripheral sensory neuromodulation plays a critical role in gating day/night-regulated
behaviors is conceptually innovative. Furthermore, in rodents, the neuronal responses to ethologically relevant odors
are also heightened at subjective nighttime. Therefore, success of this research will likely carry broad implications
across animal species.

## Key facts

- **NIH application ID:** 10995719
- **Project number:** 1R01DC021551-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Chih-Ying Su
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $504,644
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995719

## Citation

> US National Institutes of Health, RePORTER application 10995719, Olfactory neuromodulation: genes, cells, and behavior (1R01DC021551-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995719. Licensed CC0.

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