The molecular receptive range of an olfactory receptorin vivo(Drosophila melanogasterOr22a)

Abstract

Understanding how odors are coded within an olfactory system requires knowledge about its input. This is constituted by the molecular receptive ranges (MRR) of olfactory sensory neurons that converge in the glomeruli of the olfactory bulb (vertebrates) or the antennal lobe (AL, insects). Aiming at a comprehensive characterization of MRRs in Drosophila melanogaster we measured odor-evoked calcium responses in olfactory sensory neurons that express the olfactory receptor Or22a. We used an automated stimulus application system to screen [Ca(2+)] responses to 104 odors both in the antenna (sensory transduction) and in the AL (neuronal transmission). At 10(-2) (vol/vol) dilution, 39 odors elicited at least a half-maximal response. For these odorants we established dose-response relationships over their entire dynamic range. We tested 15 additional chemicals that are structurally related to the most efficient odors. Ethyl hexanoate and methyl hexanoate were the best stimuli, eliciting consistent responses at dilutions as low as 10(-9). Two substances led to calcium decrease, suggesting that Or22a might be constitutively active, and that these substances might act as inverse agonists, reminiscent of G-protein coupled receptors. There was no difference between the antennal and the AL MRR. Furthermore we show that Or22a has a broad yet selective MRR, and must be functionally described both as a specialist and a generalist. Both these descriptions are ecologically relevant. Given that adult Drosophila use approximately 43 ORs, a complete description of all MRRs appears now in reach.

Human olfactory detection of homologous n-alcohols measured via concentration–response functions

“…Notably, experiments within the same study (Oka Y et al, 2006) have shown that whereas delivery of the odorant as a vapor still needs to reach μM concentrations when the response is measured at the cell level (e.g., HEK293 or isolated olfactory sensory neurons: OSNs), it only needs to reach nM concentrations when the response is measured at the glomerular level. Thus, responses measured beyond the individual cell level, be it at the olfactory bulb (mouse) (Oka Y et al, 2006), the antennal lobe (fly) (Pelz D et al, 2006), or the integrated olfactory system (human) (this study; Cain WS et al, 2007b;Cometto-Muñiz JE et al, 2004;Wise PM et al, 2007), produce EC 50 s at or below the nM range. In terms of concentration span, the odorant response often rises from background to maximum within approximately two log units of concentration but this span can vary from one {e.g., (Kajiya K et al, 2001)} to three {e.g., (Abaffy T et al, 2006)} log units, irrespective of stimulus phase (liquid or vapor) or level at which the olfactory path is probed.…”

“…Recent studies, particularly at the receptor level, have included olfactory concentrationresponse relationships (Abaffy T et al, 2006;Jacquier V et al, 2006;Kajiya K et al, 2001;Katada S et al, 2005;Oka Y et al, 2006;Pelz D et al, 2006;Shirokova E et al, 2005). Table 3 summarizes their characteristics and those of the present work.…”

“…A main aim of these functions is to understand the physicochemical basis for the olfactory activity of vapors, and to define the chemical tuning characteristics of the sense of smell within various parts or as a whole. Recent examples of structure-activity studies exploring dose-response functions have included testing human Wise PM et al, 2007), mouse (Katada S et al, 2005;Oka Y et al, 2006), and fly (Pelz D et al, 2006;Stensmyr MC et al, 2003) olfactory responses at the receptor, cell, olfactory bulb or antennal/antennal lobe, and behavioral levels.…”

Influence of odorant receptor repertoire on odor perception in humans and fruit flies

“…We first examined the Or22a receptor, which is sensitive to esters and alcohols (6,27). Responses of flies carrying a deletion that includes the Or22a gene and genetically matched controls (22,28) were tested to 23 odors.…”

“…Responses of flies carrying a deletion that includes the Or22a gene and genetically matched controls (22,28) were tested to 23 odors. Of the odors tested, only the response to 1-heptanol, a weak agonist (27), was significantly reduced (Fig. 5A).…”