{"doi":"10.1101/2025.05.07.652728","title":"Soma to neuron communication links stress adaptation to stress avoidance behavior","abstract":"Abstract In multicellular organisms, signaling from the nervous system to the peripheral tissues can activate physiological responses to stress. Here, we show that inter-tissue stress communication can also function in reverse, i.e. from the peripheral tissue to the nervous system. osm-8 mutants, which activate the physiological osmotic stress response in the C. elegans skin, also exhibit defective osmotic avoidance (Osm) behavior, via a direct and specific effect on ASH osmosensory neuron excitability. Both osm-8 and the Patched-related gene ptr-23 , mutations in which suppress all osm-8 phenotypes, function in the hypodermal lysosomes to regulate both physiology and behavior. Unbiased lipidomics shows that osm-8 leads to a ptr-23 -dependent elevation of the lysosome specific lipid bis(monoacylglycero)phosphate (BMP) and expansion of the pool of hypodermal lysosomes. Just as genetic activation of the osmotic stress response by loss of osm-8 in the hypodermis causes an Osm phenotype, acute physiological exposure to osmotic stress also confers a reversible Osm phenotype. Behavioral and genetic plasticity requires biosynthesis of the compatible solute glycerol, a key physiological output of the organismal osmotic stress response. However, ptr-23 is only required for osm-8 induced behavioral plasticity and not physiological plasticity. Instead, both genetic and physiologically induced Osm phenotypes require the unusual non-neuronal lysosomal V-ATPase subunit vha-5 , which is also critical for organismal osmotic stress survival. Together, these data reveal that genetic or physiological activation of stress signaling from the skin elicits lysosome-associated signals that modulate organismal neurophysiology to attenuate a sensory neuron circuit. Such ‘body-brain’ interoceptive communication may allow organisms to better match neuronal decision-making with organismal physiological state.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565505,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9558,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1469184,"name":"Ella Gundrum","orcid":null,"position":1,"is_corresponding":false},{"id":1150021,"name":"María Victoria Veroli","orcid":"0000-0002-9563-3606","position":2,"is_corresponding":false},{"id":1469185,"name":"A.J. Gilsrud","orcid":null,"position":3,"is_corresponding":false},{"id":1469186,"name":"Mahdi Eskandarisani","orcid":null,"position":4,"is_corresponding":false},{"id":499879,"name":"Ioannis K. Zervantonakis","orcid":"0000-0003-2386-9553","position":5,"is_corresponding":false},{"id":1469187,"name":"Steven Mullett","orcid":null,"position":6,"is_corresponding":false},{"id":1469188,"name":"Stacy Gelhaus","orcid":null,"position":7,"is_corresponding":false},{"id":371615,"name":"Todd Lamitina","orcid":"0000-0001-7332-9075","position":8,"is_corresponding":false},{"id":1469183,"name":"Julia Witrado","orcid":null,"position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:56:28.709936Z","pmid":"40654857","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}