{"doi":"10.1101/2022.02.14.480437","title":"Insulin/IGF Signaling Regulates Presynaptic Glutamate Release in Aversive Olfactory Learning","abstract":"SUMMARY Information flow through neural circuits is continuously modified by context-dependent learning. In the nematode Caenorhabditis elegans, pairing specific odors with food deprivation results in aversion to the odor. Here we identify cell-specific mechanisms of insulin/IGF receptor signaling that integrate sensory information with food context during aversive olfactory learning. Using a conditional allele of the insulin/IGF receptor DAF-2, we show that aversive learning to butanone, an odor sensed only by the AWC ON olfactory neuron, requires DAF-2 in AWC ON . Learning requires an axonally-localized DAF-2c isoform and the insulin receptor substrate (IRS) protein IST-1, but is partly independent of the FoxO transcription factor DAF-16. Upon food deprivation, the unconditioned stimulus for learning, DAF-2 expression increases post-transcriptionally through an insulin- and ist-1- dependent process. Aversive learning suppresses odor-regulated glutamate release from AWC ON in wild-type animals but not in ist-1 mutants, suggesting that localized insulin signaling drives presynaptic depression to generate an aversive memory.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":299845,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9535,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":896188,"name":"James S. Lee","orcid":"0000-0002-4959-7237","position":1,"is_corresponding":false},{"id":896189,"name":"Maximillian Brown","orcid":"0000-0003-0547-6545","position":2,"is_corresponding":false},{"id":688919,"name":"Margaret S. Ebert","orcid":"0000-0002-9122-7854","position":3,"is_corresponding":false},{"id":896190,"name":"Masahiro Tomioka","orcid":"0000-0002-7537-714X","position":4,"is_corresponding":false},{"id":867401,"name":"Yuichi Iino","orcid":"0000-0002-0936-2660","position":5,"is_corresponding":false},{"id":688920,"name":"Cornelia I. Bargmann","orcid":"0000-0002-8484-0618","position":6,"is_corresponding":false},{"id":896187,"name":"Du Cheng","orcid":"0000-0002-7851-1244","position":0,"is_corresponding":true}],"reference_count":70,"raw_metadata":null,"created_at":"2026-07-19T00:31:49.412501Z","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":[]}