{"doi":"10.1016/j.neuron.2025.06.017","title":"Forebrain assembloids support the development of fast-spiking human PVALB+ cortical interneurons and uncover schizophrenia-associated defects","abstract":"Disruption of parvalbumin positive (PVALB+) cortical interneurons is implicated in the pathogenesis of schizophrenia. However, how these defects emerge during development remains poorly understood. The protracted, postnatal maturation of PVALB+ cortical interneurons has complicated human pluripotent stem cell (hPSC)-based models for studying their role in neuropsychiatric disease. Here, we present a forebrain assembloid system yielding PVALB+ cortical interneurons that match the molecular identity and distinctive electrophysiology of primary PVALB+ interneurons. We further established a series of isogenic hPSC lines carrying structural variants associated with schizophrenia and identified variant-specific phenotypes affecting cortical interneuron migration, the molecular profile of PVALB+ cortical interneurons, and their ability to regulate cortical network activity, including γ-band oscillations. These findings offer plausible mechanisms for how the disruption of cortical interneuron development may impact schizophrenia risk and provide a human experimental platform to study PVALB+ cortical interneurons in health and disease.","journal":"Neuron","year":2025,"id":510853,"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":18,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9486,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":747437,"name":"Gregg W. Crabtree","orcid":"0000-0002-0079-2277","position":1,"is_corresponding":false},{"id":1121378,"name":"Kriti Kalpana","orcid":"0000-0002-6664-3960","position":2,"is_corresponding":false},{"id":996184,"name":"Luz Jubierre","orcid":"0000-0001-9934-1590","position":3,"is_corresponding":false},{"id":271974,"name":"So Yeon Koo","orcid":"0000-0001-8634-7643","position":4,"is_corresponding":false},{"id":109222,"name":"Gabriele Ciceri","orcid":"0000-0002-8481-9771","position":5,"is_corresponding":false},{"id":61797,"name":"Joseph A. Gogos","orcid":"0000-0002-7491-4476","position":6,"is_corresponding":false},{"id":594915,"name":"Ilya Kruglikov","orcid":"0000-0002-1575-4636","position":7,"is_corresponding":false},{"id":109231,"name":"Lorenz Studer","orcid":"0000-0003-0741-7987","position":8,"is_corresponding":false},{"id":678634,"name":"Ryan Walsh","orcid":"0000-0003-2338-3115","position":0,"is_corresponding":true}],"reference_count":126,"raw_metadata":null,"created_at":"2026-07-19T02:47:50.575618Z","pmid":"40695284","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":[]}