PERSPECTIVE Insect olfaction from model systems to disease control Allison F. Carey and John R. Carlson1 Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520-8103 Edited by John G. Hildebrand, University of Arizona, Tucson, AZ, and approved May 23, 2011 (received for review March 12, 2011) Great progress has been made in the field of insect olfaction in recent years. Receptors, neurons, and circuits have been defined in considerable detail, and the mechanisms by which they detect, encode, and process sensory stimuli are being unraveled. We provide a guide to recent progress in the field, with special attention to advances made in the genetic model organism Drosophila. We highlight key questions that merit additional investigation. We then present our view of how recent advances may be applied to the control of disease- carrying insects such as mosquitoes, which transmit disease to hundreds of millions of people each year. We suggest how progress in defining the basic mechanisms of insect olfaction may lead to means of disrupting host-seeking and other olfactory behaviors, thereby reducing the transmission of deadly diseases. olfactory coding | odorant receptor | olfactory circuits | vector biology | pheromone he insect olfactory system has dimorphism is striking in some species. anogaster has 60 Or genes encoding 62 emerged as a prominent model For example, female Anopheles gambiae gene products through alternative splicing, fl in neuroscience. Investigation of mosquitoes possess three to four times whereas the red our beetle, Tribolium T more antennal sensilla than males (2). castaneum, has 341 predicted Ors (15). its organization and function has Such dimorphism may reflect function: Each Or is expressed within a spatially revealed surprising answers to fundamen- only female mosquitoes feed on blood, restricted subpopulation of ORNs (12–14, tal questions of how an animal detects, and they rely heavily on olfactory cues to 16). One exceptional receptor, formerly encodes, and processes sensory stimuli. locate their hosts (4). called Or83b and now called Orco, is ex- The olfactory system is also of immense Larvae of many insect species contain pressed in most ORNs of both the adult importance in the natural world, where it olfactory systems that are numerically and larval stages (12, 14, 16–21). The mediates attraction of insects to humans simpler than their adult counterparts, protein sequence of Orco is highly con- and thus underlies the transmission of perhaps reflecting the functional require- served among insect species (21–23), and ments of the two life stages. Adults often orthologs from different species can sub- disease to hundreds of millions of people fi each year. travel long distances to nd food, mates, or stitute for one another functionally (23, Remarkable progress has been made oviposition sites; they may encounter ol- 24). Orco forms a heteromer with Ors and over the past decade in elucidating mech- factory stimuli intermittently and follow is required for targeting of Ors to the anisms of insect olfaction, in many cases sparse odor gradients. By contrast, larvae ORN dendrites (21, 25, 26). More re- facilitated by the genetic tractability of the typically hatch from eggs laid directly on or cently, a surprising role for Orco in signal model organism Drosophila melanogaster. near a food source and do not navigate transduction has been identified, as Here, we consider recent advances in the over long distances. discussed below. understanding of insect olfactory re- Insect Ors are seven-transmembrane- ceptors, neurons, and circuits made in ORNs. In adults, the clustering of a small domain proteins and were long thought to Drosophila and other insect species. We number of ORNs in a sensillum allows be G protein-coupled receptors (GPCRs) present our view that this emerging body convenient physiological analysis of the like their counterparts in vertebrates and of knowledge poises the field to make cellular basis of olfaction. By inserting an C. elegans. However, in addition to lacking major contributions to the control of in- electrode into a sensillum, extracellular sequence similarity to known GPCRs, sect pests and vectors of disease, and we recordings of ORN responses to odors can their topology is inverted, with an in- highlight strategies for olfactory-based be obtained (Fig. 2C). Each ORN in a sen- tracellular N terminus and an extracellular vector control. We offer our perspec- sillum produces an action potential with C terminus (25, 27). Recent in vitro stud- tive on the most critical challenges to a characteristic relative amplitude, allowing ies indicate that the Or–Orco heteromer fi fulfilling this technological promise identi cation of the ORNs that respond functions as an odorant-gated ion channel and to solving the scientific problem of to a particular olfactory stimulus (Fig. 2D). (27–29). One of these studies provided how olfactory input is translated into Such electrophysiological recordings evidence that Orco can function as behavioral output. have revealed that different ORNs respond a channel independent of the canonical to overlapping subsets of odorants (5–7) Or, that it is stimulated by cyclic nucleo- and that the different morphological clas- tides, and that it can also signal through G Mechanisms of Insect Olfaction ses of sensilla are functionally distinct. In proteins, albeit at a slower time scale (28). Olfactory Organs. Insects sense the volatile many insect species, the ORNs of some Although there are some in vivo data chemical world with antennae (Fig. 1). single-walled sensilla respond to pher- consistent with a role for G proteins in Additional organs such as maxillary palps omones, whereas the neurons of others olfactory signaling (30), a systematic study also detect odors in many species. Olfac- are sensitive to more general odorants, of single-sensillum ORN physiology after tory organs are covered with sensory hairs such as food odors (8). The double-walled genetic manipulations of G proteins did called sensilla, each of which typically sensilla are found in many insect orders, not find evidence that they contribute to houses the dendrites of a few olfactory reflecting an ancient origin (9). They are odor sensitivity (31). receptor neurons (ORNs) (Fig. 2 A and B) often sensitive to polar compounds, in- An intriguing theme in both vertebrate (1, 2). Olfactory sensilla fall into mor- cluding amines, carboxylic acids, and water and invertebrate olfaction is that dis- phological classes, including long, single- vapor (10, 11). tinct classes of receptors continue to be walled sensilla and short, double-walled sensilla. The numbers of sensilla and Odorant Receptors. The first insect odorant ORNs per antenna vary dramatically receptors (Ors) were identified just over among species. The moth Manduca sexta a decade ago (12–14). Ors are unrelated in Author contributions: A.F.C. and J.R.C. wrote the paper. contains >100,000 antennal sensilla hous- sequence to odorant receptors of mam- The authors declare no conflict of interest. ing >250,000 ORNs, whereas ∼400 sen- mals, fish, or Caenorhabditis elegans. The This article is a PNAS Direct Submission. silla housing ∼1,200 ORNs are found in insect genomes characterized to date 1To whom correspondence should be addressed. E-mail: the D. melanogaster antenna (1, 3). Sexual contain from 60 to 341 Or genes; D. mel- [email protected]. www.pnas.org/cgi/doi/10.1073/pnas.1103472108 PNAS | August 9, 2011 | vol. 108 | no. 32 | 12987–12995 Downloaded by guest on September 29, 2021 pendence nor the transduction mechanism terns are diverse, with overlapping subsets has been defined (31). Two transient re- of OBPs found in different sensilla (45). ceptor potential (TRP) channels have The diversity of OBP expression patterns been implicated in humidity detection in and large numbers of OBPs are reminiscent D. melanogaster (36); however, it will be of odorant receptors; they suggest an in- important to resolve whether these chan- teresting role in shaping the odor response nels are humidity receptors or components profiles of ORNs within the sensilla that of downstream signaling machinery. contain them. However, when individual The most recently identified insect odorant receptors were misexpressed in receptors for odorants are related to ion- a sensillum that presumably contains a dif- otropic glutamate receptors (IRs) (37). ferent complement of OBPs than the sen- Several IRs are expressed in ORNs housed sillum in which the receptors are in the coeloconic sensilla of D. mela- endogenously expressed, the receptors nogaster, a sensillum class that, with rare conferred odor response profiles very sim- exceptions (10), does not express Ors. ilar to those observed in the endogenous Misexpression of two IRs conferred re- sensillum (46, 47). These results suggested sponses to odorants that evoked responses that odorant receptors are sufficient to from coeloconic ORNs, supporting a role confer the odor specificity of an ORN, at for IRs as receptors in these ORNs; IRs least for many receptors and many general Fig. 1. Insect antennae. (Clockwise from upper are likely to detect a variety of acids, al- odorants. However, OBPs seem likely to left) Moth (Image courtesy of Geoffrey Attardo, play roles in the dynamics of olfactory re- ’ dehydes, and amines, including ammonia Yale School of Public Health); Leconte s Scarab, (37). The sequence similarity of IRs to li- sponse and in olfactory sensitivity. Two Chrysina lecontei (Image courtesy of Alex Wild); gand-gated ion channels suggested that recent studies have reported decreased nymph of Barytettix humphreysi (Image courtesy they act as odor-gated ion channels, a hy- electrophysiological responses to odorants of Jeffrey C. Oliver); meloid beetle, Lytta magister pothesis that has recently been supported when an OBP was targeted with RNAi (48, (Image courtesy of Jeffrey C. Oliver); butterfly by functional studies (38). 49), and variations in behavioral responses (Image courtesy of Geoffrey Attardo); beetle (Im- to odorants have been associated with age courtesy of Geoffrey Attardo); ant (Image From Air to Receptor.