{"doi":"10.1016/j.celrep.2022.111685","title":"Insulin/IGF signaling regulates presynaptic glutamate release in aversive olfactory learning","abstract":"Insulin/insulin-like growth factor (IGF) receptor signaling (IIS) supports context-dependent learning in vertebrates and invertebrates. Here, we identify cell-specific mechanisms of IIS that integrate sensory information with food context to drive synaptic plasticity and learning. In the nematode Caenorhabditis elegans , pairing food deprivation with an odor such as butanone suppresses attraction to that odor. We find that aversive olfactory learning requires the insulin receptor substrate (IRS) protein IST-1 and atypical signaling through the insulin/IGF-1 receptor DAF-2. Cell-specific knockout and rescue demonstrate that DAF-2 acts in the AWC ON sensory neuron, which detects butanone, and that learning preferentially depends upon the axonally localized DAF-2c isoform. Acute food deprivation increases DAF-2 levels in AWC ON post-transcriptionally through an insulin- and insulin receptor substrate-1 ( ist-1 )-dependent process. Aversive learning alters the synaptic output of AWC ON by suppressing odor-regulated glutamate release in wild-type animals, but not in ist-1 mutants, suggesting that axonal insulin signaling regulates synaptic transmission to support aversive memory.","journal":"Cell Reports","year":2022,"id":252194,"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":24,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"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":293934,"name":"Patrick T. McGrath","orcid":"0000-0002-1598-3746","position":4,"is_corresponding":false},{"id":896190,"name":"Masahiro Tomioka","orcid":"0000-0002-7537-714X","position":5,"is_corresponding":false},{"id":867401,"name":"Yuichi Iino","orcid":"0000-0002-0936-2660","position":6,"is_corresponding":false},{"id":688920,"name":"Cornelia I. Bargmann","orcid":"0000-0002-8484-0618","position":7,"is_corresponding":false},{"id":896187,"name":"Du Cheng","orcid":"0000-0002-7851-1244","position":0,"is_corresponding":true}],"reference_count":66,"raw_metadata":null,"created_at":"2026-07-19T00:24:46.226372Z","pmid":"36417877","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":[]}