Coding of Odors by a Receptor Repertoire

SummaryWe provide a systematic analysis of how odor quality, quantity, and duration are encoded by the odorant receptor repertoire of the Drosophila antenna. We test the receptors with a panel of over 100 odors and find that strong responses are sparse, with response density dependent on chemical class. Individual receptors range along a continuum from narrowly tuned to broadly tuned. Broadly tuned receptors are most sensitive to structurally similar odorants. Strikingly, inhibitory responses are widespread among receptors. The temporal dynamics of the receptor repertoire provide a rich representation of odor quality, quantity, and duration. Receptors with similar odor sensitivity often map to widely dispersed glomeruli in the antennal lobe. We construct a multidimensional “odor space” based on the responses of each individual receptor and find that the positions of odors depend on their chemical class, concentration, and molecular complexity. The space provides a basis for predicting behavioral responses to odors

Temperature-dependent changes in the host-seeking behaviors of parasitic nematodes

Olfactory plasticity occurs in individual infective juveniles (IJs), is not affected by cultivation density, and occurs in multiple strains of Steinernema carpocapsae. A. Temperature-induced changes in sensory valence occur in individual IJs. 25 °C IJs that were repelled by 2-propanone on day 0 were collected and cultured at either 15 °C or 25 °C for 2 weeks, and then re-tested on day 14 using a modified scoring method (left). The IJs that were temperature-swapped from 25 °C to 15 °C showed opposite olfactory preferences compared to those maintained at 25 °C. *** P < 0.001, unpaired t-test; n = 6 trials for each condition. Red bar = 1 cm. B. Cultivation density does not affect temperature-induced sensory valence changes; 25 °C day 0 Ste. carpocapsae IJs were collected and stored at 15 °C at low density (1 IJ/μL), medium density (6 IJ/μL), or high density (25 IJ/μL) and tested for their response to 2-propanone and 1-hexanol after 2 weeks of storage. No significant effects of cultivation density (F 2,62 = 0.2586, P = 0.7730) or interaction (F 2,62 = 1.912, P = 0.1565) were observed in a two-way ANOVA; n = 8–18 trials for each condition. C. Multiple strains of Ste. carpocapsae exhibit temperature-dependent olfactory plasticity. In addition to the standard All strain, the DD136 and Sal strains [101] also exhibited temperature-induced sensory valence changes. A comparison of day 0 IJs that were cultured at 25 °C, day 14 IJs that were temperature-swapped from 25 °C to 15 °C on day 0, and day 14 IJs that were cultured at 25 °C revealed both temperature- and age-dependent changes in olfactory responses. ** P < 0.01; *** P < 0.001 relative to 25 °C day 0 IJs, two-way ANOVA with Dunnett’s post-test; n = 6–16 trials for each condition. For all graphs, error bars represent standard error of the mean (SEM). Mean, n, and SEM values for each assay are listed in Additional file 7: Dataset S1. (PDF 529 kb

Feeding state sculpts a circuit for sensory valence in Caenorhabditis elegans

Hunger affects the behavioral choices of all animals, and many chemosensory stimuli can be either attractive or repulsive depending on an animal’s hunger state. Although hunger-induced behavioral changes are well documented, the molecular and cellular mechanisms by which hunger modulates neural circuit function to generate changes in chemosensory valence are poorly understood. Here, we use the CO_2 response of the free-living nematode Caenorhabditis elegans to elucidate how hunger alters valence. We show that CO_2 response valence shifts from aversion to attraction during starvation, a change that is mediated by two pairs of interneurons in the CO_2 circuit, AIY and RIG. The transition from aversion to attraction is regulated by biogenic amine signaling. Dopamine promotes CO_2 repulsion in well-fed animals, whereas octopamine promotes CO_2 attraction in starved animals. Biogenic amines also regulate the temporal dynamics of the shift from aversion to attraction such that animals lacking octopamine show a delayed shift to attraction. Biogenic amine signaling regulates CO_2 response valence by modulating the CO_2-evoked activity of AIY and RIG. Our results illuminate a new role for biogenic amine signaling in regulating chemosensory valence as a function of hunger state

Targeted mutagenesis in a human-parasitic nematode.

Parasitic nematodes infect over 1 billion people worldwide and cause some of the most common neglected tropical diseases. Despite their prevalence, our understanding of the biology of parasitic nematodes has been limited by the lack of tools for genetic intervention. In particular, it has not yet been possible to generate targeted gene disruptions and mutant phenotypes in any parasitic nematode. Here, we report the development of a method for introducing CRISPR-Cas9-mediated gene disruptions in the human-parasitic threadworm Strongyloides stercoralis. We disrupted the S. stercoralis twitchin gene unc-22, resulting in nematodes with severe motility defects. Ss-unc-22 mutations were resolved by homology-directed repair when a repair template was provided. Omission of a repair template resulted in deletions at the target locus. Ss-unc-22 mutations were heritable; we passed Ss-unc-22 mutants through a host and successfully recovered mutant progeny. Using a similar approach, we also disrupted the unc-22 gene of the rat-parasitic nematode Strongyloides ratti. Our results demonstrate the applicability of CRISPR-Cas9 to parasitic nematodes, and thereby enable future studies of gene function in these medically relevant but previously genetically intractable parasites

Feeding state sculpts a circuit for sensory valence in Caenorhabditis elegans

Hunger affects the behavioral choices of all animals, and many chemosensory stimuli can be either attractive or repulsive depending on an animal’s hunger state. Although hunger-induced behavioral changes are well documented, the molecular and cellular mechanisms by which hunger modulates neural circuit function to generate changes in chemosensory valence are poorly understood. Here, we use the CO_2 response of the free-living nematode Caenorhabditis elegans to elucidate how hunger alters valence. We show that CO_2 response valence shifts from aversion to attraction during starvation, a change that is mediated by two pairs of interneurons in the CO_2 circuit, AIY and RIG. The transition from aversion to attraction is regulated by biogenic amine signaling. Dopamine promotes CO_2 repulsion in well-fed animals, whereas octopamine promotes CO_2 attraction in starved animals. Biogenic amines also regulate the temporal dynamics of the shift from aversion to attraction such that animals lacking octopamine show a delayed shift to attraction. Biogenic amine signaling regulates CO_2 response valence by modulating the CO_2-evoked activity of AIY and RIG. Our results illuminate a new role for biogenic amine signaling in regulating chemosensory valence as a function of hunger state

Olfaction shapes host–parasite interactions in parasitic nematodes

Many parasitic nematodes actively seek out hosts in which to complete their lifecycles. Olfaction is thought to play an important role in the host-seeking process, with parasites following a chemical trail toward host-associated odors. However, little is known about the olfactory cues that attract parasitic nematodes to hosts or the behavioral responses these cues elicit. Moreover, what little is known focuses on easily obtainable laboratory hosts rather than on natural or other ecologically relevant hosts. Here we investigate the olfactory responses of six diverse species of entomopathogenic nematodes (EPNs) to seven ecologically relevant potential invertebrate hosts, including one known natural host and other potential hosts collected from the environment. We show that EPNs respond differentially to the odor blends emitted by live potential hosts as well as to individual host-derived odorants. In addition, we show that EPNs use the universal host cue CO_2 as well as host-specific odorants for host location, but the relative importance of CO_2 versus host-specific odorants varies for different parasite–host combinations and for different host-seeking behaviors. We also identified host-derived odorants by gas chromatography-mass spectrometry and found that many of these odorants stimulate host-seeking behaviors in a species-specific manner. Taken together, our results demonstrate that parasitic nematodes have evolved specialized olfactory systems that likely contribute to appropriate host selection

Receptor-type guanylate cyclase is required for carbon dioxide sensation by Caenorhabditis elegans

CO_2 is both a critical regulator of animal physiology and an important sensory cue for many animals for host detection, food location, and mate finding. The free-living soil nematode Caenorhabditis elegans shows CO_2 avoidance behavior, which requires a pair of ciliated sensory neurons, the BAG neurons. Using in vivo calcium imaging, we show that CO_2 specifically activates the BAG neurons and that the CO_2-sensing function of BAG neurons requires TAX-2/TAX-4 cyclic nucleotide-gated ion channels and the receptor-type guanylate cyclase GCY-9. Our results delineate a molecular pathway for CO_2 sensing and suggest that activation of a receptor-type guanylate cyclase is an evolutionarily conserved mechanism by which animals detect environmental CO_2

Olfactory circuits and behaviors of nematodes

Over one billion people worldwide are infected with parasitic nematodes. Many parasitic nematodes actively search for hosts to infect using volatile chemical cues, so understanding the olfactory signals that drive host seeking may elucidate new pathways for preventing infections. The free-living nematode Caenorhabditis elegans is a powerful model for parasitic nematodes: because sensory neuroanatomy is conserved across nematode species, an understanding of the microcircuits that mediate olfaction in C. elegans may inform studies of olfaction in parasitic nematodes. Here we review circuit mechanisms that allow C. elegans to respond to odorants, gases, and pheromones. We also highlight work on the olfactory behaviors of parasitic nematodes that lays the groundwork for future studies of their olfactory microcircuits