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

Abstract

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 .guanylyl cyclase | olfaction | transcriptional profiling | regulator of G protein signaling | chemosensation T he ability to detect and respond to changing concentrations of environmental CO 2 is widespread among animals and plays a critical role in locating food, finding hosts and mates, and avoiding danger (1-4). CO 2 exposure can also have profound physiological effects, including altered respiration, motility, fecundity, and emotional state (5-7). CO 2 is sensed as an aversive cue by many free-living animals, including humans (3,6,8,9). By contrast, many parasites and disease vectors are attracted to CO 2 , which serves as a sensory cue for host location (1, 10).Nematodes constitute a large and highly diverse phylum that includes both free-living and parasitic species. Many parasitic nematodes, including some of the most devastating human-and plant-parasitic nematodes, are attracted to CO 2 . By contrast, adults of the free-living species Caenorhabditis elegans are repelled by CO 2 (11-14). CO 2 avoidance by C. elegans requires a pair of head neurons called the BAG neurons (13), which also mediate responses to decreases in ambient oxygen levels (15). Whether the BAG neurons directly sense CO 2 is not known, and the signaling pathways that mediate CO 2 detection are poorly understood.We show here that environmental CO 2 specifically activates the BAG neurons and not other neurons that drive avoidance behavior, suggesting that the BAG neurons are primary sensory neurons that detect CO 2 . Prolonged CO 2 exposure causes desensitization of avoidance behavior and the BAG neurons themselves, indicating that behavioral adaptation to CO 2 occurs at the level of the BAG neurons. In addition, we show that the CO 2 -evoked activity of the BAG neurons requires a cGMP signaling pathway consisting of the receptor guanylate cyclase GCY-9 and the cGMP-gated cation channel TAX-2/TAX-4. Insects detect CO 2 using a pair of gustatory receptors (16, 17), whereas some mammals detect CO 2 using the receptor-type guanylate cyclase, guanylate cyclase D (GC-D), and soluble adenylate cyclase (18)(19)(20). Our results show that the mechanism of CO 2 detection in C. elegans more closely resembles that of mammals than insects and suggest an evolutionarily ancient role for receptor-type guanyl...

Environmental CO 2 inhibits Caenorhabditis elegans egg-laying by modulating olfactory neurons and evokes widespread changes in neural activity

“…These imaging results were unexpected, especially because previous studies failed to detect CO 2 -evoked Ca 2+ responses in the nociceptive ADL (6) and ASH neurons (5,6). Such discrepancies may reflect differences in stimulus regimes, imaging conditions, Ca 2+ indicators, or transgenic lines used.…”

“…Only one chemosensory transducer of CO 2 has been identified in C. elegans, GCY-9, which is required for CO 2 sensitivity in BAG neurons (6). The inherent complexity of CO 2 as a stimulus and the numerous molecules whose activity is sensitive to CO 2 /H + in vitro (3) led us to conjecture that C. elegans has undiscovered CO 2 -sensing neurons and pathways.…”

“…The ubiquity of CO 2 suggests that the ecologically relevant information it communicates will depend on the dynamics of the CO 2 stimulus and on context. CO 2 -responsive excitable cells have been identified in mammals (3), arthropods (4), and nematodes (5,6). However, the number of CO 2 -responsive neurons that are functional in vivo, how they are embedded in neural circuits, and how they shape behavior is unclear.…”

“…Three neurons that respond robustly to CO 2 have been identified thus far in this animal: BAG neurons that also respond to O 2 , the thermosensory AFD neurons, and the gustatory ASE neurons (5,6). CO 2 responses in BAG neurons are mediated by a receptor-type guanylate cyclase, GCY-9, that signals via a cGMP-gated ion channel encoded by the tax-2 and tax-4 genes (6).…”

Reciprocal inhibition between sensory ASH and ASI neurons modulates nociception and avoidance in Caenorhabditis elegans

“…Notably, the neurotransmitters, such as neuropeptides, serotonin (5-HT), tyramine (TA) and octopamine (OA), have been increasingly shown to be transmitters or modulators of ASH-mediated aversive behaviours [12][13][14][15] . ASI sensory neurons are reported to mediate dauer formation 16 , enable worms to learn to avoid the smell of pathogenic bacteria after ingestion via INS-6 signalling 17 , suppress male-specific sexual attraction behaviour 18 , respond to temperature stimuli to negatively modulate thermotaxis behaviour 19 , mediate diet-restriction-induced longevity 20 , modulate satiety quiescence 21 , regulate acute CO 2 avoidance 22 , repress exploratory behaviours that comprise spontaneous reversals and omega turns 5 , and inhibit ASH-mediated aversive responses to 100% 1-octanol 23 . These studies support the hypothesis that ASIs are important polymodal sensory neurons mediating or modulating worm behaviours and development.…”