The broad long-term objective of this research is to elucidate the function of the volatile pheromone-detecting neurons expressing orphan odorant receptors. Volatile pheromones trigger or modulate social behaviors including mating. This work is significant because understanding pheromone biology in Drosophila will translate into new methods to control reproduction in insects that transmit human diseases and destroy crops and will shed new insights into the circuits guiding social behavior in an animal model system. Using a multifaceted approach that includes genetics, chemistry, electrophysiology, behavior and imaging we will identify ligands for these receptors, determine the behavioral effects of inactivating and activating these individual neural circuits, and map the downstream circuits activated by these neurons.
The first aim i s to determine the behaviors influenced through neurons expressing Or83c, which we have identified as a receptor for farnesol.
The second aim i s to identify ligands that trigger changes in activity in ten orphan trichoid receptors using the 'empty trichoid neuron'system, localize the endogenous neurons expressing these receptors, and characterize their downstream signal transduction requirements.
The third aim i s to identify behaviors modulated by activation or inactivation of these circuits triggered by odorant stimulation of these receptors.
Aim 4 is to map the synaptic targets of the second order projection neurons innervating the trichoid glomeruli using the MARCM approach to begin to trace the neuroanatomy of these behavioral circuits. The completion of the studies will advance our understanding of volatile pheromone biology in an important model system, will identify new targets to manipulate insect behavior, and will guide future studies on pheromone signaling in more complex animal model systems.

Public Health Relevance

Pheromones mediate social behaviors in insects. Insects carry human diseases that kill millions of people every year;malaria alone accounts for over one million deaths annually. Many insect behaviors, including mating, are triggered by pheromones, therefore understanding pheromone biology will provide new targets to manipulate pheromone signals, with the long-term goal of blocking mating in pathogenic insects. We propose to explore the function of orphan pheromone receptors to understand what they do and how they work and what neuronal circuits they activate. The results of these studies will guide future social behavioral experiments in more complex vertebrate animals.

National Institute of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Research Project (R01)
Project #
Application #
Study Section
Molecular Neuropharmacology and Signaling Study Section (MNPS)
Program Officer
Sullivan, Susan L
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Texas Sw Medical Center Dallas
Schools of Medicine
United States
Zip Code
Guo, Hao; Kunwar, Kishor; Smith, Dean (2017) Odorant Receptor Sensitivity Modulation in Drosophila. J Neurosci 37:9465-9473
Pitts, Svetlana; Pelser, Elizabeth; Meeks, Julian et al. (2016) Odorant Responses and Courtship Behaviors Influenced by at4 Neurons in Drosophila. PLoS One 11:e0162761
You, Yinwei; Smith, Dean P; Lv, Mingyue et al. (2016) A broadly tuned odorant receptor in neurons of trichoid sensilla in locust, Locusta migratoria. Insect Biochem Mol Biol 79:66-72
Ha, Tal Soo; Xia, Ruohan; Zhang, Haiying et al. (2014) Lipid flippase modulates olfactory receptor expression and odorant sensitivity in Drosophila. Proc Natl Acad Sci U S A 111:7831-6
Ronderos, David S; Lin, Chun-Chieh; Potter, Christopher J et al. (2014) Farnesol-detecting olfactory neurons in Drosophila. J Neurosci 34:3959-68
Lvovskaya, Svetlana; Smith, Dean P (2013) A spoonful of bitter helps the sugar response go down. Neuron 79:612-4
Li, Qingyun; Ha, Tal Soo; Okuwa, Sumie et al. (2013) Combinatorial rules of precursor specification underlying olfactory neuron diversity. Curr Biol 23:2481-90
Sanders, Charcacia; Smith, Dean P (2011) LUMP is a putative double-stranded RNA binding protein required for male fertility in Drosophila melanogaster. PLoS One 6:e24151
Kwon, Young; Kim, Sang Hoon; Ronderos, David S et al. (2010) Drosophila TRPA1 channel is required to avoid the naturally occurring insect repellent citronellal. Curr Biol 20:1672-8