Chih-Ying Su - US grants

PROJECT SUMMARY/ABSTRACT The long-term goal of this project is to reveal the mechanisms by which complex odors are encoded, with a special focus on the initial stages of olfactory information processing. The research design takes advantage of the anatomical simplicity and powerful genetic toolkit of Drosophila melanogaster, which allows systematic molecular genetic analysis of olfactory circuits as well as in-depth physiological and behavioral analysis of olfactory function. The results may have major implications for the control of insect vectors of disease. The project focuses on ephaptic interactions, a novel, non-synaptic form of olfactory circuit communication, which take place between any two grouped olfactory receptor neurons (ORNs) housed in the same insect sensory hair (sensillum). Despite its ubiquity, how ephaptic communication regulates olfactory function and behavior is poorly understood. We recently provided the first description of the importance of ephaptic inhibition in insect olfaction. In the current study, we will first focus on defining the importance of ephaptic excitation. A systematic, functional survey will be performed to define the strength of ephaptic excitation between grouped ORNs (Aim 1). The respective electrotonic properties of grouped ORNs will also be determined (Aim 2). The strength of ephaptic interactions will be quantified between a pair of ORNs from both directions with a view to testing the hypothesis that ephaptic interactions are asymmetric across sensillum types. Furthermore, the ultrastructure of grouped ORNs will be described using serial block-face electron microscopy (SBEM) and 3D reconstruction imaging technologies (Aim 3). This Aim is designed to identify the biophysical factors that underlie asymmetric ephaptic interactions in a sensillum. Morphological features of an identified ORN, such as dendritic caliber, number of dendritic branches, as well as soma size, will be analyzed and compared between neighboring ORNs. The hypothesis that the physically larger ORN in a pair exerts stronger ephaptic interactions upon its neighbor will be tested. This Aim could also lead to critical technical breakthroughs to broaden the application of SBEM in illuminating the 3D ultrastructure of any identified cell in diverse tissues. Lastly, the functional importance of ephaptic interactions in odor-guided behavior will be determined (Aim 4). Specifically, we will extend our behavioral assay and define the role of ephaptic inhibition on courtship behavior in sensillum which houses ORNs responsive to pheromone cues. We will also perform the first test of the functional importance of ephaptic excitation between another ORN pair that mediates behavioral responses to food odors. The proposed research will determine the functional importance and biophysical principles of a novel form of olfactory circuit interaction mechanism. These findings have the potential to revolutionize our understanding of olfactory information processing in insects, and may reveal general principles that govern chemosensory behavior throughout the animal kingdom.

PROJECT SUMMARY/ABSTRACT 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.

PROJECT SUMMARY/ABSTRACT The goal of this project is to determine the organizing principle underlying olfactory receptor neuron (ORN) grouping in the antennal sensory hairs of Drosophila. For most sensory systems, neurons are arranged in an ordered manner to form topographic representations of stimuli from the external world. Understanding the organizing principle of such maps is critical for deciphering the nature of salient features that are extracted from parallel inputs through lateral inhibition. However in olfaction, whether and how neurons are organized into a sensory map remains largely unclear. In both rodents and flies, it is reported that neighboring glomeruli do not necessarily respond to similar odorants. In the absence of a chemotopic map, what then is the organizing principle for the olfactory system? To address this complex question, the research outlined here leverages the powerful genetic toolkit and tractable olfactory system of Drosophila. The general hypothesis? that ORNs are organized in the periphery based on the hedonic value of their detected odors to form a valence map?will be tested via systematic behavioral assays with optogenetic or thermogenetic activation of select receptor neurons. The proposal?s first aim is to determine the generality of the observation that in the same sensory hair, compartmentalized ORNs mediate opposing behavior?with attraction elicited by activation of the large-spike ORN(s) and aversion by the small-spike neighbor(s). The remaining aims propose to examine this organizing principle in sensory hairs implicated in regulating female egg-laying (Aim 2) or male courtship behavior (Aim 3). Successful execution of the proposal will likely bridge a longstanding knowledge gap in sensory biology by revealing, for the first time, olfactory maps within a complex organism.