{"doi":"10.17615/drqs-9631","title":"Spine pruning drives antipsychotic-sensitive locomotion via circuit control of striatal dopamine","abstract":"Psychiatric and neurodevelopmental disorders may arise from anomalies in long-range neuronal connectivity downstream of pathologies in dendritic spines. However, the mechanisms that may link spine pathology to circuit abnormalities relevant to atypical behavior remain unknown. Using a mouse model to conditionally disrupt a critical regulator of the dendritic spine cytoskeleton, Arp2/3, we report here a molecular mechanism that unexpectedly reveals the interrelationship of progressive spine pruning, elevated frontal cortical excitation of pyramidal neurons, and striatal hyperdopaminergia within a cortical-to-midbrain circuit abnormality. The main symptomatic manifestations of this circuit abnormality are psychomotor agitation and stereotypical behaviors, which are relieved by antipsychotics. Moreover, antipsychotic-responsive locomotion can be directly mimicked in wildtype mice by optogenetic activation of this circuit. Collectively these results reveal molecular and neural-circuit mechanisms, illustrating how diverse pathologies may converge to drive behaviors relevant to psychiatric disorders.","journal":"UNC Libraries","year":2020,"id":143763,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9531,"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":351417,"name":"Namsoo Kim","orcid":"0000-0003-3083-8835","position":1,"is_corresponding":false},{"id":303897,"name":"Scott H. Soderling","orcid":"0000-0001-7808-197X","position":2,"is_corresponding":false},{"id":364659,"name":"Richard J. Weinberg","orcid":"0000-0001-9689-7278","position":3,"is_corresponding":false},{"id":522159,"name":"Bence Rácz","orcid":"0000-0002-1933-5332","position":4,"is_corresponding":false},{"id":351424,"name":"Henry H. Yin","orcid":"0000-0003-1546-6850","position":5,"is_corresponding":false},{"id":612252,"name":"Dipendra K. Aryal","orcid":null,"position":6,"is_corresponding":false},{"id":464313,"name":"Il Hwan Kim","orcid":"0000-0002-4225-002X","position":7,"is_corresponding":false},{"id":284547,"name":"Fan Wang","orcid":"0000-0003-2988-0614","position":8,"is_corresponding":false},{"id":611875,"name":"Akiyoshi Uezu","orcid":"0000-0001-8478-4460","position":9,"is_corresponding":false},{"id":258568,"name":"William C. Wetsel","orcid":"0000-0002-3592-7397","position":10,"is_corresponding":false},{"id":250221,"name":"Mark A. Rossi","orcid":"0000-0002-5724-3615","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:17:41.821196Z","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":[]}