{"doi":"10.1101/2020.07.09.196428","title":"Synchronous and opponent thermosensors use flexible cross-inhibition to orchestrate thermal homeostasis","abstract":"Body temperature homeostasis is an essential function that relies upon the integration of the outputs from multiple classes of cooling- and warming-responsive cells. The computations that integrate these diverse outputs to control body temperature are not understood. Here we discover a new set of Warming Cells (WCs), and show that the outputs of these WCs and previously described Cooling Cells (CCs 1 ) are combined in a cross-inhibition computation to drive thermal homeostasis in larval Drosophila . We find that WCs and CCs are opponent sensors that operate in synchrony above, below, and near the homeostatic set-point, with WCs consistently activated by warming and inhibited by cooling, and CCs the converse. Molecularly, these opponent sensors rely on overlapping combinations of Ionotropic Receptors to detect temperature changes: Ir68a, Ir93a, and Ir25a for WCs; Ir21a, Ir93a, and Ir25a for CCs. Using a combination of optogenetics, sensory receptor mutants, and quantitative behavioral analysis, we find that the larva uses flexible cross-inhibition of WC and CC outputs to locate and stay near the homeostatic set-point. Balanced cross-inhibition near the set-point suppresses any directed movement along temperature gradients. Above the set-point, WCs mediate avoidance to warming while cross-inhibiting avoidance to cooling. Below the set-point, CCs mediate avoidance to cooling while cross-inhibiting avoidance to warming. Our results demonstrate how flexible cross-inhibition between warming and cooling pathways can orchestrate homeostatic thermoregulation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":122455,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9433,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":563654,"name":"Alicia Chen","orcid":"0000-0001-5521-8566","position":1,"is_corresponding":false},{"id":506035,"name":"Gonzalo Budelli","orcid":"0000-0002-2157-5511","position":2,"is_corresponding":false},{"id":563655,"name":"Vincent Richter","orcid":"0000-0001-8009-0357","position":3,"is_corresponding":false},{"id":563656,"name":"Anna Rist","orcid":"0000-0001-7634-1432","position":4,"is_corresponding":false},{"id":563657,"name":"Andreas S. Thum","orcid":"0000-0002-3830-6596","position":5,"is_corresponding":false},{"id":556227,"name":"Mason Klein","orcid":"0000-0001-8211-077X","position":6,"is_corresponding":false},{"id":563658,"name":"Paul Garrity","orcid":"0000-0002-8274-6564","position":7,"is_corresponding":false},{"id":233156,"name":"Aravinthan D. T. Samuel","orcid":"0000-0002-1672-8720","position":8,"is_corresponding":false},{"id":559178,"name":"Luis Hernandez-Nunez","orcid":"0000-0003-3102-9036","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-18T23:14:51.076430Z","pmid":null,"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":[]}