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Insect Olfaction: A Map of Smell in the Brain

2005; Elsevier BV; Volume: 15; Issue: 17 Linguagem: Inglês

10.1016/j.cub.2005.08.033

1879-0445

Gregory S.X.E. Jefferis,

Insect and Arachnid Ecology and Behavior

Humans use three classes of photoreceptor to span the visible spectrum, but smell relies on hundreds of distinct classes of olfactory receptor neuron. Even the simple fruitfly has around 50 classes of olfactory receptor neuron. Two new studies map the projections of the great majority of these neurons into stereotyped positions in the fly brain, giving us an almost complete atlas of olfactory information transfer. Humans use three classes of photoreceptor to span the visible spectrum, but smell relies on hundreds of distinct classes of olfactory receptor neuron. Even the simple fruitfly has around 50 classes of olfactory receptor neuron. Two new studies map the projections of the great majority of these neurons into stereotyped positions in the fly brain, giving us an almost complete atlas of olfactory information transfer. Odour molecules are detected when they bind to a cognate seven transmembrane receptor located on the dendrites of olfactory receptor neurons (ORNs). This activates a G-protein signalling cascade, producing an action potential that travels down the axon to the brain. The pioneering of work of Buck and Axel [1Buck L. Axel R. A novel multigene family may encode odorant receptors: a molecular basis for odor recognition.Cell. 1991; 65: 175-181Abstract Full Text PDF PubMed Scopus (3446) Google Scholar] identified the first members of what has turned out to be a very large family of olfactory receptor genes — over a thousand in mice (reviewed in [2Mombaerts P. Seven-transmembrane proteins as odorant and chemosensory receptors.Science. 1999; 286: 707-711Crossref PubMed Scopus (349) Google Scholar]). In Drosophila the 50 or so classes of olfactory receptor neuron are dispersed into two external sensory structures, the third antennal segment and the maxillary palp (Figure 1A ). There are about 1300 ORNs on each side of the brain that send axons to the antennal lobe, the fly's equivalent of the mammalian olfactory bulb. Two principles have emerged from work on vertebrate olfaction—the central dogma of olfactory molecular biology, as it were: first, each neuron expresses only one type of receptor. Second, each glomerulus is the site of convergence of only one type of receptor neuron (Figure 2A ). It should be emphasised though that the evidence for these assertions remains indirect — no one has actually done the heroic experiment of attempting to probe individual receptor neurons for all the hundreds of receptors they could possibly express. Two new studies in this issue of Current Biology [3Fishilevich Y. Vosshall L.B. Genetic and functional subdivision of the Drosophila antennal lobe.Curr. Biol. 2005; 15 (this issue): 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar, 4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] now provide an almost complete molecular map of the olfactory system of the fruitfly. By generating a series of transgenic flies in which discrete ORN classes have been labelled, Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] and Fishilevich and Vosshall [3Fishilevich Y. Vosshall L.B. Genetic and functional subdivision of the Drosophila antennal lobe.Curr. Biol. 2005; 15 (this issue): 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar] have been able to determine almost the entire set of connections that relay olfactory information from the fly's antennae to its brain. For the general biologist, these data confirm the organisational principles outlined above for a whole sensory system; for the specialist, they provide a treasure trove of information that will inform studies of development, functional organisation and evolution of the olfactory system. The completion of the Drosophila genome sequence enabled a number of groups to identify a family of olfactory receptor genes (OR family) [5Clyne P.J. Certel S.J. de Bruyne M. Zaslavsky L. Johnson W.A. Carlson J.R. The odor specificities of a subset of olfactory receptor neurons are governed by Acj6, a POU-domain transcription factor.Neuron. 1999; 22: 339-347Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 6Gao Q. Chess A. Identification of candidate Drosophila olfactory receptors from genomic DNA sequence.Genomics. 1999; 60: 31-39Crossref PubMed Scopus (360) Google Scholar, 7Vosshall L.B. Amrein H. Morozov P.S. Rzhetsky A. Axel R. A spatial map of olfactory receptor expression in the Drosophila antenna.Cell. 1999; 96: 725-736Abstract Full Text Full Text PDF PubMed Scopus (827) Google Scholar]. The most up-to-date genomic analysis suggests that there are 60 olfactory receptor genes encoding 62 different proteins [8Robertson H.M. Warr C.G. Carlson J.R. Molecular evolution of the insect chemoreceptor gene superfamily in Drosophila melanogaster.Proc. Natl. Acad. Sci. USA. 2003; 100: 14537-14542Crossref PubMed Scopus (513) Google Scholar]. To visualise olfactory receptor gene expression Gal4 lines are used to drive expression of a reporter gene under the control of a given olfactory receptor promoter. Two earlier studies examined the axonal projection patterns revealed by a total of five OR genes [9Gao Q. Yuan B. Chess A. Convergent projections of Drosophila olfactory neurons to specific glomeruli in the antennal lobe.Nat. Neurosci. 2000; 3: 780-785Crossref PubMed Scopus (485) Google Scholar, 10Vosshall L.B. Wong A.M. Axel R. An olfactory sensory map in the fly brain.Cell. 2000; 102: 147-159Abstract Full Text Full Text PDF PubMed Scopus (760) Google Scholar]. In line with vertebrate data, the conclusion was that neurons expressing a particular receptor send axons to one or in some cases two glomeruli in the antennal lobe. The first surprise came from the observation that one receptor, Or83b, is actually expressed in all ORNs; it appears to be required for OR trafficking, as it does not confer odour sensitivity itself [11Larsson M.C. Domingos A.I. Jones W.D. Chiappe M.E. Amrein H. Vosshall L.B. Or83b encodes a broadly expressed odorant receptor essential for Drosophila olfaction.Neuron. 2004; 43: 703-714Abstract Full Text Full Text PDF PubMed Scopus (846) Google Scholar]. Of the two groups, Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] took a slightly more comprehensive approach and made Gal4 lines for all 62 olfactory receptor transcripts, while the other group made 49. Between them they have mapped the expression of 46 olfactory receptors to 37 glomerular targets with almost complete consistency. In this accounting, there are more receptors than glomeruli. Is this fact indicative of co-expression of receptors or co-convergence at a single glomerulus of more than one class of ORNs (Figure 2B)? It has already been documented that one pair of evolutionarily distant receptors are functionally co-expressed in a maxillary palp neuron [12de Bruyne M. Foster K. Carlson J.R. Odor coding in the Drosophila antenna.Neuron. 2001; 30: 537-552Abstract Full Text Full Text PDF PubMed Scopus (520) Google Scholar]. Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] find evidence for four more cases of co-expression of what appear to be recently duplicated olfactory receptor genes and argue that these are likely to encode functionally similar odorant receptors. Fishilevich and Vosshall [3Fishilevich Y. Vosshall L.B. Genetic and functional subdivision of the Drosophila antennal lobe.Curr. Biol. 2005; 15 (this issue): 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar] did not check those four particular cases, but identified four additional cases of co-expression — a point of difference among these otherwise very consistent studies. Perhaps the difference reflects the sensitivity of their expression assays. In conclusion, 'one receptor, one neuron' is essentially the rule. Many of the exceptions seem due to recent gene duplication events. However, some functionally significant co-expression may exist. Ultimately, it will be necessary to test whether co-expression has any functional significance by asking whether manipulating the receptor expression of neurons alters their odour response profile. Fishilevich and Vosshall [3Fishilevich Y. Vosshall L.B. Genetic and functional subdivision of the Drosophila antennal lobe.Curr. Biol. 2005; 15 (this issue): 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar] make a good argument that in two of the four cases the second odorant receptor may be inhibitory, sharpening the tuning properties of the neuron by counteracting a more promiscuous receptor. What about co-convergence? Both groups observe that glomerulus VA6 is the target of neurons labelled by two different odorant receptor Gal4 lines but their interpretation differs; Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] argue that it is due to ectopic expression of one Gal4 line. Thus, in Drosophila a given glomerulus is the target of a single ORN population with only very rare exceptions. Fishilevich and Vosshall [3Fishilevich Y. Vosshall L.B. Genetic and functional subdivision of the Drosophila antennal lobe.Curr. Biol. 2005; 15 (this issue): 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar] show that odorant receptor transgenes are expressed in discrete zones in the antenna. When the location of ORNs in the antenna is compared with the location of their axonal projections in the antennal lobe, a broad tendency is observed: medial–proximal regions of the antenna tend to map to medial regions of the lobe and lateral–distal regions of the antenna tend to map to lateral regions of the antennal lobe. However, there are many exceptions to this rule and it is clear that there is not a one-to-one topographic map that is transferred from the antenna to the antennal lobe. Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] characterise the molecular organisation of antennal sensilla. These are the sensory bristles that contain between two and four ORNs and are classified by shape as basiconic, trichoid or coeloconic (Figure 1B). Amazingly, physiological studies have suggested that ORNs with distinct odour response profiles are always located in a particular sensillum [12de Bruyne M. Foster K. Carlson J.R. Odor coding in the Drosophila antenna.Neuron. 2001; 30: 537-552Abstract Full Text Full Text PDF PubMed Scopus (520) Google Scholar, 13Goldman A.L. Van der Goes van Naters W. Lessing D Warr C.G. Carlson J.R. Coexpression of two functional odor receptors in one neuron.Neuron. 2005; 45: 661-666Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar, 14Hallem E.A. Ho M.G. Carlson J.R. The molecular basis of odor coding in the Drosophila antenna.Cell. 2004; 117: 965-979Abstract Full Text Full Text PDF PubMed Scopus (579) Google Scholar]. For example, sensilla of class ab1 contain a quartet of neurons highly sensitive to isoamyl acetate (banana), 2,3-butanedione (butter or stale sweat), CO2 and methyl salicylate (wintergreen mint) (Figure 1B,C). Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] identified the molecular identity of 38 neuronal classes distributed among 13 different basiconic and four trichoid sensilla. Curiously, only one odorant receptor construct mapped to a coeloconic sensillum; perhaps these neurons express an unidentified family of chemosensory receptors. In conjunction with other physiological data, this allowed them to determine which odorant receptor is responsible for which odour response profile. The logic behind why specific classes of ORNs are located together in the same sensilla is not obvious and in particular they are not more closely related by sequence or odour specificity than random groups of ORNs. One clear feature of antennal lobe organisation emerging from the new data is a correlation between sensory organ anatomy and projection position — the projections of neurons from the three major classes of sensilla are spatially distinct. In particular, ORNs from trichoid sensilla project as a group into the dorsolateral region of the lobe, an area that is quite reminiscent of the male specific macroglomerular complex of moths. Notably, trichoid sensilla are known to contain pheromone-sensitive ORNs in some moths. Furthermore, some of the glomeruli that are targeted by ORNs from trichoid sensilla are known to be sexually dimorphic in size and targets of neurons expressing the male form of the Drosophila fruitless gene [15Stockinger P. Kvitsiani D. Rotkopf S. Tirian L. Dickson B.J. Neural circuitry that governs Drosophila male courtship behavior.Cell. 2005; 121: 795-807Abstract Full Text Full Text PDF PubMed Scopus (389) Google Scholar]. It will be of great interest to see if they play a significant role in mate recognition. The target glomeruli for ORNs from basiconic and coeloconic sensilla are clustered medially and posteriorly, respectively, while the target glomeruli of maxillary palp ORNs are clustered in a central anterior region. Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] also observed a significant relationship between olfactory receptor sequence similarity and position in the antennal lobe; similar receptors cluster to some extent. Is there any evidence for functional topography in the antennal lobe? In vertebrates, there is evidence for a spatial gradient of responsiveness, for example to aldehydes with different carbon chain lengths— a phenomenon known as 'chemotopy' [16Meister M. Bonhoeffer T. Tuning and topography in an odor map on the rat olfactory bulb.J. Neurosci. 2001; 21: 1351-1360PubMed Google Scholar]. Fishilevich and Vosshall [3Fishilevich Y. Vosshall L.B. Genetic and functional subdivision of the Drosophila antennal lobe.Curr. Biol. 2005; 15 (this issue): 1548-1553Abstract Full Text Full Text PDF PubMed Scopus (396) Google Scholar] cautiously note a progression from 'generalist' to 'specialist' for ORNs targeting glomeruli from dorsomedial to ventrolateral positions in the antennal lobe. Couto et al. [4Couto A. Alenius M. Dickson B.J. Molecular, anatomical, and functional organization of the Drosophila olfactory system.Curr. Biol. 2005; 15 (this issue): 1535-1547Abstract Full Text Full Text PDF PubMed Scopus (614) Google Scholar] are more upbeat arguing for clustering of glomeruli sensitive to aromatic compounds and in particular for a chemotopic axis from posterior to anterior with increasing carbon chain length of esters, compounds frequently associated with ripe fruit. The 'one receptor, one neuron' and 'one receptor, one glomerulus' rules have now been tested for almost the entire peripheral olfactory system of Drosophila. The broad-brush conclusion is that both rules are correct, but that there are a small number of exceptions in which olfactory receptors are co-expressed in the same neuron. There is evidence for some degree of functional organisation of the antennal lobe both at the level of olfactory receptor sequence similarity and chemotopy, while the evidence for clustering of projections by sensillar type is quite convincing. The newly established molecular cartography will serve as an important reference for years to come and should ensure that future behavioural, physiological or developmental studies refer to specific olfactory receptor neurons with confidence.