Olfactory circuits and behaviors of nematodes

Abstract

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.

Figure 1. Models of microcircuit motifs present in the C. elegans olfactory system

A. A feedback inhibition motif promotes odor adaptation and possibly gain control [23]. The AWC olfactory neurons release NLP-1, which binds NPR-11 on AIA interneurons to inhibit their activity. In the presence of an odor, AWC activity is suppressed. The resulting decrease in NLP-1 signaling permits AIA to release INS-1, which inhibits AWC through an unknown receptor [23]. B. Odor environment modulates feeding through a reciprocal inhibition motif [39]. The presence of attractive odors increases feeding, while the presence of repulsive odors decreases feeding. The attractive odorant diacetyl is sensed by the AWA neurons and causes serotonin (5-HT) release from the NSM neurons. 5-HT binds the serotonin-gated chloride channel MOD-1 on the RIM and RIC interneurons, which inhibits them and increases feeding. Repellents such as quinine or high concentrations of isoamyl alcohol (IAA) are sensed by the ASH neurons and promote release of octopamine (OA) and tyramine (TA) from RIM and RIC. OA and TA bind the SER-2 receptor on the NSM neurons and inhibit serotonin release [39].

Figure 2. Diverse responses to CO₂ across nematode species

A. CO₂ chemotaxis behavior varies across nematode species [84]. Phoretic C. elegans dauers, which seek insect vectors, entomopathogenic Ste. carpocapsae IJs, and passively ingested H. contortus IJs are attracted to CO₂, while skin-penetrating Str. stercoralis IJs are repelled by CO₂ [51,84]. Dauers and IJs were tested in a chemotaxis assay with 10% CO₂, in which the animals were given 1 hr to migrate in a CO₂ gradient. A positive chemotaxis index (CI) indicates attraction and a negative CI indicates repulsion. B. The BAG neurons are required for multiple CO₂-evoked behaviors across species. Left, BAG neurons are required for CO₂ chemotaxis in C. elegans adults and dauers regardless of whether CO₂ is attractive or repulsive [37,51]. BAG-ablated C. elegans adults were tested in a 20 min assay [37], whereas dauers were tested in a 10 min assay [51]. Right, BAG neurons are required for both CO₂ chemotaxis and CO₂-evoked jumping in Ste. carpocapsae IJs [51]. The BAG neurons in IJs were laser-ablated; wild-type animals were mock-ablated. IJs were tested in either a 1 hr chemotaxis assay or a jumping assay in which IJs were given 8 s to jump in response to a 10% CO₂ puff [51]. C. The response of Ste. scapterisci IJs to CO₂ shifts from repulsion to attraction as the IJs age [90]. IJs were tested in a 1 hr chemotaxis assay with 1% CO₂.

Figure 3. Olfactory responses of parasitic nematodes reflect their host ranges and infection modes rather than their genetic relatedness

A. Schematic of phylogenetic relationships among nematode species [65,84]. Phylogenetic analysis is based on Castelletto et al., 2014 [84] and Dillman et al., 2012 [65]. B. A behavioral dendrogram of odor preferences among nematode species [84]. Species cluster based on the hosts they infect and their modes of infection, rather than their genetic relationships. For example, the skin-penetrating rat parasites Str. ratti and N. brasiliensis show similar odor preferences, even though they are not closely related genetically [84].