{"doi":"10.1101/2024.01.30.578027","title":"Arc mediates intercellular synaptic plasticity via IRSp53-dependent extracellular vesicle biogenesis","abstract":"Abstract Current models of learning and memory have focused on cell-autonomous regulation of synaptic strength; however, intercellular signaling between cells in the brain is critical for normal cognition. The immediate early gene Arc is a repurposed retrotransposon critical for long-term forms of synaptic plasticity and memory. Arc protein forms virus-like capsids released in extracellular vesicles (EVs) that signal cell-to-cell. Here, we find that long-term potentiation (LTP) stimuli induce the biogenesis of Arc EVs by recruiting the I-BAR protein IRSp53 to dendrites, which facilitates Arc capsid assembly and release. Arc EVs transfer Arc protein and mRNA to neighboring neurons, where translation of transferred Arc mRNA induces a loss of surface AMPA-type glutamate receptors. These results show that Arc EVs mediate non-cell autonomous long-term depression (LTD), revealing an intercellular form of synaptic plasticity that may be critical for memory consolidation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":484391,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1326582,"name":"Kaelan Sullivan","orcid":null,"position":1,"is_corresponding":false},{"id":646269,"name":"J. R. Einstein","orcid":"0000-0002-4250-1554","position":2,"is_corresponding":false},{"id":349170,"name":"Sevnur Kömürlü Keceli","orcid":null,"position":3,"is_corresponding":false},{"id":645806,"name":"Tom Kicmal","orcid":"0000-0001-7673-4690","position":4,"is_corresponding":false},{"id":1326072,"name":"Mitali Tyagi","orcid":"0000-0002-0447-4364","position":5,"is_corresponding":false},{"id":274113,"name":"Michael P. Hantak","orcid":"0000-0003-4431-4135","position":6,"is_corresponding":false},{"id":1326583,"name":"Tate Shepherd","orcid":null,"position":7,"is_corresponding":false},{"id":1326584,"name":"Alyson Stewart","orcid":null,"position":8,"is_corresponding":false},{"id":1326585,"name":"Kenneth Lyon","orcid":null,"position":9,"is_corresponding":false},{"id":1326073,"name":"Adarsh Dharan","orcid":"0000-0001-7047-826X","position":10,"is_corresponding":false},{"id":1326586,"name":"Thomas Gallagher","orcid":null,"position":11,"is_corresponding":false},{"id":329247,"name":"Edward M. Campbell","orcid":"0000-0001-5665-9195","position":12,"is_corresponding":false},{"id":465468,"name":"Jason D. Shepherd","orcid":"0000-0001-7384-8289","position":13,"is_corresponding":false},{"id":1006168,"name":"Alicia Ravens","orcid":null,"position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":null,"created_at":"2026-07-19T02:07:38.055693Z","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":[]}