{"doi":"10.1101/2025.05.08.652787","title":"Neuropeptide signalling and perineurial barrier generate a persistent stress-induced internal state in <i>Drosophila</i>","abstract":"Abstract Although fear conditioning has elucidated cue-evoked acute fear responses, the mechanisms by which stress experiences induce generalized internal states linked to anxiety are poorly understood. Here, we report that robust stress induces a persistent behavioral change characterized by avoidance of a confined space, claustrophobia-like behavior in Drosophila . Unlike aversive memory formation, the development of claustrophobia-like behavior does not require dopamine receptors. Our neuronal screening determined that neuropeptide signalling via Allatostatin-A inactivates the downstream neurons via its receptor AstA-R1, causally inducing claustrophobia-like behavior. Moreover, gene expression profiling of individual fly heads revealed that immune response activation in perineurial barrier is involved in claustrophobia-like behavior. Our data demonstrate that stress-induced persistent behavioral change would not be related to a canonical mechanism of aversive memory formation, rather involves neuropeptidergic signalling and perineurial barrier, providing the mechanism determining internal states which persistently change behavioral modes.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":565872,"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":0.957,"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":311772,"name":"Xinyue Hu","orcid":"0000-0002-2508-121X","position":1,"is_corresponding":false},{"id":1116262,"name":"Yuzhe Gu","orcid":"0009-0007-3302-8244","position":2,"is_corresponding":false},{"id":1469399,"name":"Guangnan Tian","orcid":"0000-0001-9952-766X","position":3,"is_corresponding":false},{"id":1469400,"name":"Julie L. Semmelhack","orcid":"0000-0002-8154-264X","position":4,"is_corresponding":false},{"id":1469764,"name":"Kokoro Saito","orcid":null,"position":5,"is_corresponding":false},{"id":991878,"name":"Hiromu Tanimoto","orcid":"0000-0001-5880-6064","position":6,"is_corresponding":false},{"id":1469401,"name":"Koki Tsuyuzaki","orcid":"0000-0003-3797-2148","position":7,"is_corresponding":false},{"id":361689,"name":"Shintaro Naganos","orcid":"0000-0002-5540-557X","position":8,"is_corresponding":false},{"id":1116267,"name":"Tomoyuki Miyashita","orcid":"0009-0007-0436-5073","position":9,"is_corresponding":false},{"id":361694,"name":"Minoru Saitoe","orcid":"0000-0001-9731-4214","position":10,"is_corresponding":false},{"id":759804,"name":"Yukinori Hirano","orcid":"0000-0003-3313-637X","position":11,"is_corresponding":false},{"id":759802,"name":"Abdalla G. Alia","orcid":"0000-0001-9165-842X","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-19T02:56:32.546082Z","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":[]}