The long-term goal of this project is to determine the molecular mechanisms by which sex-determining genes and reproductive hormones differentially regulate olfactory sensitivity in males and females. In humans, olfactory performance is highly dependent on age and sex; women generally outperform men in smell identification, and men are more prone to olfactory impairment as they age. Similarly, in other animal species, select groups of odorant receptor neurons (ORNs), such as those important for pheromone detection, exhibit sexually dimorphic characteristics as animals reach the age of sexual maturity. However, the mechanisms underlying sexually-dimorphic neurophysiology are poorly understood.The research outlined here takes advantage of the powerful genetic toolkit of the Drosophila olfactory system to address this complex question. In this proposal, the first aim is to determine the generality of age-dependent sensitization in courtship- promoting ORNs. The hypothesis that all courtship-promoting ORNs in males undergo age-dependent sensitization will be tested using genetic, pharmacological, and functional imaging approaches.
The second aim proposes a genetic analysis of downstream effector molecules that enhance olfactory sensitivity in the courtship-promoting ORNs. Finally, the third aim will test the hypothesis that a reproductive hormone promotes age-dependent sensitization through its interaction with a male-specific transcription factor. Results from these studies are expected to yield critical mechanistic insights into how sex-determining genes and reproductive hormones jointly regulate sensory neurophysiology and olfactory processing. These insights may have implications in understanding sexually dimorphic neurophysiology and sex-specific proclivities for certain neurodegenerative diseases.

Public Health Relevance

In humans, men and women generally exhibit different olfactory sensitivity and acuity, as well as different rates of olfactory decline as they age. Using Drosophila olfaction as a model, our project aims to determine the molecular mechanisms by which age and sex impact olfactory function in a sexually dimorphic manner. The mechanistic insights expected from this research have the potential to shed light on sex-specific proclivities for certain neurodegenerative diseases .

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
1R01DC016466-01
Application #
9376656
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2017-07-01
Project End
2022-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093