{"doi":"10.7554/elife.67065","title":"Mechanism for differential recruitment of orbitostriatal transmission during actions and outcomes following chronic alcohol exposure","abstract":"Psychiatric disease often produces symptoms that have divergent effects on neural activity. For example, in drug dependence, dysfunctional value-based decision-making and compulsive-like actions have been linked to hypo- and hyperactivity of orbital frontal cortex (OFC)-basal ganglia circuits, respectively; however, the underlying mechanisms are unknown. Here we show that alcohol-exposed mice have enhanced activity in OFC terminals in dorsal striatum (OFC-DS) associated with actions, but reduced activity of the same terminals during periods of outcome retrieval, corresponding with a loss of outcome control over decision-making. Disrupted OFC-DS terminal activity was due to a dysfunction of dopamine-type 1 receptors on spiny projection neurons (D1R SPNs) that resulted in increased retrograde endocannabinoid signaling at OFC-D1R SPN synapses reducing OFC-DS transmission. Blocking CB1 receptors restored OFC-DS activity in vivo and rescued outcome-based control over decision-making. These findings demonstrate a circuit-, synapse-, and computation-specific mechanism gating OFC activity in alcohol-exposed mice.","journal":"eLife","year":2021,"id":170710,"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":27,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9502,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":703713,"name":"Christian Cazares","orcid":"0000-0002-8899-2109","position":1,"is_corresponding":false},{"id":703714,"name":"Emily T. Baltz","orcid":"0000-0001-9770-3666","position":2,"is_corresponding":false},{"id":703715,"name":"Drew C. Schreiner","orcid":"0000-0001-6596-4415","position":3,"is_corresponding":false},{"id":703716,"name":"Ege A Yalcinbas","orcid":"0000-0002-9480-7192","position":4,"is_corresponding":false},{"id":262509,"name":"Thomas Steinkellner","orcid":"0000-0003-4591-4992","position":5,"is_corresponding":false},{"id":262516,"name":"Thomas S. Hnasko","orcid":"0000-0001-6176-8513","position":6,"is_corresponding":false},{"id":484669,"name":"Christina M. Gremel","orcid":"0000-0002-8710-0543","position":7,"is_corresponding":false},{"id":703712,"name":"Rafael Renteria","orcid":"0000-0002-6199-0293","position":0,"is_corresponding":true}],"reference_count":98,"raw_metadata":null,"created_at":"2026-07-18T23:46:24.040760Z","pmid":"33729155","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":[]}