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We use the robust locomotory responses of\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    to high levels of H\n                    <jats:sub>2<\/jats:sub>\n                    S to elucidate the molecular mechanisms underlying its acute and adaptive responses. We find that the H\n                    <jats:sub>2<\/jats:sub>\n                    S-evoked behavioral response is shaped by multiple environmental factors including oxygen (O\n                    <jats:sub>2<\/jats:sub>\n                    ) levels and nutritional state and is modulated by various pathways such as insulin, TGF-\u03b2, and HIF-1 signaling, as well as by input from O\n                    <jats:sub>2<\/jats:sub>\n                    -sensing neurons. Prolonged exposure to H\n                    <jats:sub>2<\/jats:sub>\n                    S activates HIF-1 signaling, leading to the upregulation of stress-responsive genes, including those involved in H\n                    <jats:sub>2<\/jats:sub>\n                    S detoxification. This promotes an adaptive state in which locomotory speed is reduced in H\n                    <jats:sub>2<\/jats:sub>\n                    S, while responsiveness to other stimuli is preserved. In mutants deficient in HIF-1 signaling, iron storage, and detoxification mechanisms, animals display a robust initial response but rapidly enter a sleep-like behavior characterized by reduced mobility and diminished responsiveness to subsequent sensory stimuli. Furthermore, while acute production of mitochondria-derived reactive O\n                    <jats:sub>2<\/jats:sub>\n                    species (ROS) appears to initiate the avoidance response to H\n                    <jats:sub>2<\/jats:sub>\n                    S, persistently high ROS promotes an adaptive state, likely by activating various stress-response pathways, without substantially compromising cellular H\n                    <jats:sub>2<\/jats:sub>\n                    S detoxification capacity. Taken together, our study provides comprehensive molecular insights into the mechanisms through which\n                    <jats:italic>C. elegans<\/jats:italic>\n                    modulates and adapts its response to H\n                    <jats:sub>2<\/jats:sub>\n                    S exposure.\n                  <\/jats:p>","DOI":"10.7554\/elife.92964","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T08:54:41Z","timestamp":1703667281000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.92964","source":"Crossref","is-referenced-by-count":0,"title":["Avoidance of hydrogen sulfide is modulated by external and internal states in Caenorhabditis elegans"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0239-8732","authenticated-orcid":true,"given":"Longjun","family":"Pu","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05kb8h459","id-type":"ROR","asserted-by":"publisher"}],"name":"Department 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