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1.  Molecular determinants of odorant receptor function in insects 
Journal of biosciences  2014;39(4):555-563.
The olfactory system of Drosophila melanogaster provides a powerful model to study molecular and cellular mechanisms underlying function of a sensory system. In the 1970s Siddiqi and colleagues pioneered the application of genetics to olfactory research and isolated several mutant Drosophila with odorant-specific defects in olfactory behaviour, suggesting that odorants are detected differentially by the olfactory system. Since then basic principles of olfactory system function and development have emerged using Drosophila as a model. Nearly four decades later we can add computational methods to further our understanding of how specific odorants are detected by receptors. Using a comparative approach we identify two categories of short amino acid sequence motifs: ones that are conserved family-wide predominantly in the C-terminal half of most receptors, and ones that are present in receptors that detect a specific odorant, 4-methylphenol, found predominantly in the N-terminal half. The odorant-specific sequence motifs are predictors of phenol detection in Anopheles gambiae and other insects, suggesting they are likely to participate in odorant binding. Conversely, the family-wide motifs are expected to participate in shared functions across all receptors and a mutation in the most conserved motif leads to a reduction in odor response. These findings lay a foundation for investigating functional domains within odorant receptors that can lead to a molecular understanding of odor detection.
PMCID: PMC4385708  PMID: 25116610
Drosophila; motifs; odor receptor; olfaction
2.  Inhibition among olfactory receptor neurons 
Often assumed to be epiphenomena of a cell’s activity, extracellular currents and resulting potential changes are increasingly recognized to influence the function of other cells in the vicinity. Experimental evidence shows that even small electric fields can modulate spike timing in neurons. Moreover, when neurons are brought close together experimentally or in pathological conditions, activity in one neuron can excite its neighbors. Inhibitory ephaptic mechanisms, however, may depend on more specialized coupling among cells. Recent studies in the Drosophila olfactory system have shown that excitation of a sensory neuron can inhibit its neighbor, and it was speculated that this interaction was ephaptic. Here we give an overview of ephaptic interactions that effect changes in spike timing, excitation or inhibition in diverse systems with potential relevance to human neuroscience. We examine the mechanism of the inhibitory interaction in the Drosophila system and that of the well-studied ephaptic inhibition of the Mauthner cell in more detail. We note that both current towards and current away from the local extracellular environment of a neuron can inhibit it, but the mechanism depends on the specific architecture of each system.
PMCID: PMC3805947  PMID: 24167484
olfaction; inhibition; ephaptic; sensillum; sensory neurons; Drosophila
3.  Generalization of courtship learning in Drosophila is mediated by cis-vaccenyl acetate 
Current biology : CB  2007;17(7):599-605.
Reproductive behavior in Drosophila has both stereotyped and plastic components that are driven by age- and sex-specific chemical cues. Males who unsuccessfully court virgin females subsequently avoid females that are of the same age as the trainer. In contrast, males trained with mature mated females associate volatile appetitive and aversive pheromonal cues and learn to suppress courtship of all females. Here we show that the volatile aversive pheromone that leads to generalized learning with mated females is (Z)-11-octadecenyl acetate (cis-vaccenyl acetate, cVA). cVA is a major component of the male cuticular hydrocarbon profile, but it is not found on virgin females. During copulation, cVA is transferred to the female in ejaculate along with sperm and peptides that decrease her sexual receptivity. When males sense cVA (either synthetic or from mated female or male extracts) in the context of female pheromone, they develop a generalized suppression of courtship. The effects of cVA on initial courtship of virgin females can be blocked by expression of tetanus toxin in Or65a, but not Or67d neurons, demonstrating that the aversive effects of this pheromone are mediated by a specific class of olfactory neuron. These findings suggest that transfer of cVA to females during mating may be part of the male’s strategy to suppress reproduction by competing males.
PMCID: PMC1913718  PMID: 17363250
Learning and memory; olfaction; Drosophila; pheromones; cis-vaccenyl acetate
4.  Receptors and neurons for fly odors in Drosophila 
Current biology : CB  2007;17(7):606-612.
Remarkably little is known about the molecular and cellular basis of mate recognition in Drosophila [1]. We systematically examine one of the three major types of sensilla that house olfactory receptor neurons (ORNs) on the Drosophila antenna, the trichoid sensilla, by electrophysiological analysis. We find that none respond strongly to food odors, but all respond to fly odors. Two subtypes of trichoid sensilla contain ORNs that respond to cis-vaccenyl acetate (cVA), an anti-aphrodisiac pheromone present in males and transferred to females during mating [2–4]. All trichoid sensilla yield responses to a male extract; a subset yield responses to a virgin female extract as well. Thus males can be distinguished from virgin females by the activity they elicit among the trichoid ORN population. We then systematically test all members of the Odor receptor (Or) gene family [5–7] that are expressed in trichoid sensilla [8], using an in vivo expression system [9]. Four receptors respond to fly odors in this system: two respond to extracts of both males and virgin females, and two respond to cVA. We propose a model for how these receptors might be used by a male to distinguish suitable from unsuitable mating partners through a simple logic.
PMCID: PMC1876700  PMID: 17363256
5.  Mechanisms of odor receptor gene choice in Drosophila 
Neuron  2007;53(3):353-369.
A remarkable problem in neurobiology is how olfactory receptor neurons (ORNs) select, from among a large odor receptor repertoire, which receptors to express. We use computational algorithms and mutational analysis to define positive and negative regulatory elements that are required for selection of odor receptor (Or) genes in the proper olfactory organ of Drosophila, and we identify an element that is essential for selection in one ORN class. Two odor receptors are coexpressed by virtue of the alternative splicing of a single gene, and we identify dicistronic mRNAs that each encode two receptors. Systematic analysis reveals no evidence for negative feedback regulation, but provides evidence that the choices made by neighboring ORNs of a sensillum are coordinated via the asymmetric segregation of regulatory factors from a common progenitor. We show that receptor gene choice in Drosophila also depends on a combinatorial code of transcription factors to generate the receptor-to-neuron map.
PMCID: PMC1986798  PMID: 17270733
Olfaction; Drosophila; odor receptor gene; antenna

Results 1-5 (5)