{"doi":"10.1101/2020.01.20.896233","title":"Cocaine Triggers Glial-Mediated Synaptogenesis","abstract":"Abstract Synaptogenesis is essential in forming new neurocircuits during development, and this is mediated in part by astrocyte-released thrombospondins (TSPs) and activation of their neuronal receptor, α2δ-1. Here, we show that this developmental synaptogenic mechanism is utilized during cocaine experience to induce spinogenesis and the generation of AMPA receptor-silent glutamatergic synapses in the adult nucleus accumbens (NAc). Specifically, cocaine administration activates NAc astrocytes, and preventing this activation blocks cocaine-induced generation of silent synapses. Furthermore, knockout of TSP2, or pharmacological inhibition or viral-mediated knockdown of α2δ-1, prevents cocaine-induced generation of silent synapses. Moreover, disrupting TSP2-α2δ-1-mediated spinogenesis and silent synapse generation in the NAc occludes cue-induced cocaine seeking after withdrawal from cocaine self-administration and cue-induced reinstatement of cocaine seeking after drug extinction. These results establish that silent synapses are generated by an astrocyte-mediated synaptogenic mechanism in response to cocaine experience and embed critical cue-associated memory traces that promote cocaine relapse.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":121932,"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":0.961,"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":298268,"name":"King-Lun Li","orcid":"0000-0001-5636-5939","position":1,"is_corresponding":false},{"id":300140,"name":"Avani Shukla","orcid":null,"position":2,"is_corresponding":false},{"id":298269,"name":"Anna Beroun","orcid":"0000-0003-4376-5241","position":3,"is_corresponding":false},{"id":300141,"name":"Masago Ishikawa","orcid":null,"position":4,"is_corresponding":false},{"id":298270,"name":"Xiaojie Huang","orcid":"0000-0001-9499-8294","position":5,"is_corresponding":false},{"id":298271,"name":"Yao Wang","orcid":"0000-0002-1855-6280","position":6,"is_corresponding":false},{"id":455129,"name":"Yao Wang","orcid":"0000-0002-9631-8309","position":7,"is_corresponding":false},{"id":300142,"name":"Yao Q. Wang","orcid":null,"position":8,"is_corresponding":false},{"id":300143,"name":"Noah D. Bastola","orcid":null,"position":10,"is_corresponding":false},{"id":298273,"name":"Hugh H. Huang","orcid":"0000-0002-6523-0101","position":11,"is_corresponding":false},{"id":298274,"name":"Lily E. Kramer","orcid":"0000-0001-7312-8521","position":12,"is_corresponding":false},{"id":300144,"name":"Terry Chao","orcid":null,"position":13,"is_corresponding":false},{"id":298275,"name":"Yanhua H. Huang","orcid":"0000-0003-1770-0196","position":14,"is_corresponding":false},{"id":298276,"name":"Susan R. Sesack","orcid":"0000-0002-2852-7440","position":15,"is_corresponding":false},{"id":196103,"name":"Eric J. Nestler","orcid":"0000-0002-7905-2000","position":16,"is_corresponding":false},{"id":298277,"name":"Oliver M. Schlüter","orcid":"0000-0001-8958-5815","position":17,"is_corresponding":false},{"id":298278,"name":"Yan Dong","orcid":"0000-0003-0016-9028","position":18,"is_corresponding":false},{"id":298267,"name":"Junshi Wang","orcid":"0000-0002-2290-3759","position":0,"is_corresponding":true}],"reference_count":87,"raw_metadata":null,"created_at":"2026-07-18T23:14:46.979435Z","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":[]}