Advantage of the Highly Restricted Odorant Receptor Expression Pattern in Chemosensory Neurons of Drosophila.

A fundamental molecular feature of olfactory systems is that individual neurons express only one receptor from a large odorant receptor gene family. While numerous theories have been proposed, the functional significance and evolutionary advantage of generating a sophisticated one-receptor-per neuron expression pattern is not well understood. Using the genetically tractable Drosophila melanogaster as a model, we demonstrate that the breakdown of this highly restricted expression pattern of an odorant receptor in neurons leads to a deficit in the ability to exploit new food sources. We show that animals with ectopic co-expression of odorant receptors also have a competitive disadvantage in a complex environment with limiting food sources. At the level of the olfactory system, we find changes in both the behavioral and electrophysiological responses to odorants that are detected by endogenous receptors when an olfactory receptor is broadly misexpressed in chemosensory neurons. Taken together these results indicate that restrictive expression patterns and segregation of odorant receptors to individual neuron classes are important for sensitive odor-detection and appropriate olfactory behaviors

Larvae co-expressing <i>Or42a</i> in multiple neurons show reduced survival and failure to exploit a secondary food source in a competitive environment.

<p>Mean cumulative rates of eclosion from 50 embryos each of <i>(42a4)-Gal4</i> (green line, control) and <i>(42a4)-Gal4;UAS-Or42a</i> (magenta line, co-expressing) plotted for days after egg laying in (<b>A</b>) a primary limiting food source, and (<b>B</b>) a primary and a secondary limiting food source. (<b>C</b>) Percentage of larvae accumulating on the second food source at 5 days after egg laying. (<b>D</b>) Mean cumulative rates of eclosion from competition between 50 embryos of the two genotypes when presented in a primary and secondary limiting food source as in (<b>B</b>). Arrowhead indicates half-maximal eclosion rate for each genotype, T-test, *<i>P</i><0.05, **<i>P</i><0.01, N = 6 trials, error bars = s.e.m.</p

Behavioral responses to some attractive odors is different in larvae co-expressing <b><i>Or42a</i></b><b> in multiple neurons.</b>

<p>The mean preference index (PI) of larvae towards attractive odor (10⁻²) is depicted. N = 8 trials, ∼50 larvae/trial, error bars = s.e.m., T-test, **<i>P</i><0.01.</p

A mutated <b><i>Or42a</i></b><b> promoter can drive expression in multiple chemosensory neurons in the larvae.</b>

<p>(<b>A</b>) Confocal micrograph Z-projections of olfactory neurons with dendrites innervating the Dome sensillum seen as fluorescent dome structure called the Dorsal Organ, and putative gustatory neurons (marked with arrowheads) with dendrites innervating the Terminal Organ in larvae expressing <i>UAS-mcd8:GFP</i> under the control of the wild-type <i>Or42a-Gal4</i> or mutant <i>(42a4)-Gal4 </i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0066173#pone.0066173-Ray1" target="_blank">[6]</a> (<b>B</b>) Mean number of neurons innervating the Dorsal Organ (DO) and Terminal Organ (TO) in the indicated genotypes. N = 7 (Or42a-Gal4) and N = 13 ((42a4)-Gal4), error bars = s.e.m., T-test, **<i>P</i><0.0001. (<b>C</b>) Representative confocal Z-projections from larval brains of indicated genotypes. (<b>D</b>) Zoomed in view of a larval antennal lobe from <i>(42a4)-Gal4; UAS-mcd8:GFP</i> counterstained with nc82 (red). (<b>E</b>) Mean number of glomeruli labeled by <i>UAS-mcd8:GFP</i> driven by the indicated promoters. N = 6 for each sample, error bars = s.e.m., T-test, **<i>P</i><0.01.</p

Electrodomogram (EDG) recordings from the larval dome sensillum of larvae co-expressing <b><i>Or42a</i></b><b> in multiple nuerons.</b>

<p>Mean EDG response (<b>A</b>) trace and (<b>B</b>) response to 0.5 sec pulse of indicated odorants (10⁻²). N = 6–8, error bars = s.e.m, T-test, **<i>P</i><0.01.</p

Advantage of the Highly Restricted Odorant Receptor Expression Pattern in Chemosensory Neurons of <i>Drosophila</i>

<div><p>A fundamental molecular feature of olfactory systems is that individual neurons express only one receptor from a large odorant receptor gene family. While numerous theories have been proposed, the functional significance and evolutionary advantage of generating a sophisticated one-receptor-per neuron expression pattern is not well understood. Using the genetically tractable <i>Drosophila melanogaster</i> as a model, we demonstrate that the breakdown of this highly restricted expression pattern of an odorant receptor in neurons leads to a deficit in the ability to exploit new food sources. We show that animals with ectopic co-expression of odorant receptors also have a competitive disadvantage in a complex environment with limiting food sources. At the level of the olfactory system, we find changes in both the behavioral and electrophysiological responses to odorants that are detected by endogenous receptors when an olfactory receptor is broadly misexpressed in chemosensory neurons. Taken together these results indicate that restrictive expression patterns and segregation of odorant receptors to individual neuron classes are important for sensitive odor-detection and appropriate olfactory behaviors.</p></div

Odour receptors and neurons for DEET and new insect repellents.

There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure-activity screen of &gt;400,000 compounds that identified &gt;100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide

Odour receptors and neurons for DEET and new insect repellents

There are major impediments to finding improved DEET alternatives because the receptors causing olfactory repellency are unknown, and new chemicals require exorbitant costs to determine safety for human use. Here we identify DEET-sensitive neurons in a pit-like structure in the Drosophila melanogaster antenna called the sacculus. They express a highly conserved receptor, Ir40a, and flies in which these neurons are silenced or Ir40a is knocked down lose avoidance to DEET. We used a computational structure-activity screen of &gt;400,000 compounds that identified &gt;100 natural compounds as candidate repellents. We tested several and found that most activate Ir40a(+) neurons and are repellents for Drosophila. These compounds are also strong repellents for mosquitoes. The candidates contain chemicals that do not dissolve plastic, are affordable and smell mildly like grapes, with three considered safe in human foods. Our findings pave the way to discover new generations of repellents that will help fight deadly insect-borne diseases worldwide