This project?s long-term goal is a fuller understanding of the neurobiological mechanisms of olfactory sensory adaptation that facilitate odor discrimination in the natural world. To confront the wide fluctuations in intensity and temporal variability that are characteristic of natural odor environments, animals have evolved refined neurosensory mechanisms for parsing behaviorally-relevant signals such as pheromones from background nuisance odors. This project seeks to elucidate how adaptive mechanisms in the olfactory periphery play a central role in this discrimination task. The project will utilize a novel behavioral assay that permits precise quantification of the logic used by insects in navigating complex, temporally dynamic odor environments. By combining this assay with data analytic methods and machine learning, a comprehensive lexicon of archetypal navigational strategies of insect odor navigation will be derived. Importantly, since both odors and insects can be simultaneously tracked in this assay, the project will uncover strategies employed by insects in not just static, but also fluctuating odor landscapes. By quantifying how these strategies modulate in time, the role of memory in shaping navigational strategies will also be determined. The project will then leverage this dictionary of navigational logic to quantify how various mechanisms of adaptation in Drosophila olfactory receptor neurons can shape odor discrimination. Importantly, this project will examine the role of olfactory sensory adaptation in an ethologically-relevant way, by connecting mechanisms that operate at the level of sensory input with neural computations that affect output behavior. Further, since the behavioral assay tracks complex odor environments simultaneous with freely-moving insects, the impact of behavior on future signal acquisition ? behavioral feedback onto odor stimuli ? is fully maintained. The behavioral experiments and data analysis in this project utilize the tractable, highly-characterized system of Drosophila melanogaster, in which a wealth of existing genetic tools will allow directed experimentation of specific adaptive mechanisms in olfaction. The results of this project will elucidate how insects effectively navigate complex odor environments, and how olfactory systems maintain sensitivity despite odor conflicts and temporal variability.

Public Health Relevance

This project will contribute to our understanding of how the olfactory sensory periphery and neural circuitry have evolved to effectively encode our vast and varied chemical environment. The project will help reveal how odor discrimination capability is maintained in natural odor landscapes, leading to practical interventional strategies for the control of disease vectors such as tsetse flies and mosquitos, who rely critically on their sense of smell to navigate. Chemical sensing is the only shared sensation among organisms as simple as bacteria and as complex as humans, and this project will enhance our fundamental knowledge of this universal sensory modality.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32MH118700-01
Application #
9667825
Study Section
Special Emphasis Panel (ZMH1)
Program Officer
Van'T Veer, Ashlee V
Project Start
2019-03-01
Project End
2022-02-28
Budget Start
2019-03-01
Budget End
2020-02-28
Support Year
1
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Yale University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520