{"doi":"10.64898/2025.12.17.694950","title":"Mecp2 deficiency impairs microscale cortical network topology and dynamics in a Rett syndrome mouse model","abstract":"loss-of-function mutations. Mecp2-deficient mouse models reveal disruptions of microscale cortical circuits. Yet how cellular-scale information processing is altered in Mecp2-deficient microscale functional networks is unknown. We investigated the development of functional connectivity, network topology, and dynamics in microelectrode array (MEA) recordings of primary cortical cultures from Mecp2-deficient and wild-type mice. Mecp2-deficient cortical networks developed more slowly and showed decreased functional connectivity compared to wild-type, leading to smaller network size, density, and strength of connectivity. Altered network topological features in Mecp2-deficient microscale circuits predicted decreased efficiency and information-sharing capacity. This reveals developmental deficits in microscale functional networks, which may in turn underlie the cortical decline and severe cognitive disability in Rett syndrome. These findings also offer circuit-level targets and an in-vitro approach for evaluating new therapeutic products for restoring microscale network function.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":585909,"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":0.9499,"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":1234191,"name":"Timothy P.H. Sit","orcid":"0000-0003-1149-0466","position":1,"is_corresponding":false},{"id":1234192,"name":"Rachael C. Feord","orcid":"0000-0001-7801-8137","position":2,"is_corresponding":false},{"id":1500079,"name":"Asma Soltani","orcid":null,"position":3,"is_corresponding":false},{"id":642402,"name":"Yuan Yin","orcid":"0000-0002-0467-8092","position":4,"is_corresponding":false},{"id":1499736,"name":"Richard Turner","orcid":"0000-0003-1672-4022","position":5,"is_corresponding":false},{"id":1500080,"name":"Ines Loureiro","orcid":null,"position":6,"is_corresponding":false},{"id":73036,"name":"Stephen J. Eglen","orcid":"0000-0001-8607-8025","position":7,"is_corresponding":false},{"id":606954,"name":"Ole Paulsen","orcid":"0000-0002-2258-5455","position":8,"is_corresponding":false},{"id":1234201,"name":"Susanna B. Mierau","orcid":"0000-0002-1220-6423","position":9,"is_corresponding":false},{"id":1234193,"name":"Alexander WE Dunn","orcid":"0000-0003-1504-499X","position":0,"is_corresponding":true}],"reference_count":40,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:59:24.273134Z","pmid":"41446258","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":[]}