{"doi":"10.1101/2021.02.05.429987","title":"Somatostatin-positive Interneurons Contribute to Seizures in <i>SCN8A</i> Epileptic Encephalopathy","abstract":"Abstract SCN8A epileptic encephalopathy is a devastating epilepsy syndrome caused by mutant SCN8A which encodes the voltage-gated sodium channel Na V 1.6. To date, it is unclear if and how inhibitory interneurons, which express Na V 1.6, influence disease pathology. We found that selective expression of the R1872W mutation in somatostatin (SST) interneurons was sufficient to convey susceptibility to audiogenic seizures. SST interneurons from mutant mice were hyperexcitable but hypersensitive to action potential failure via depolarization block under normal and seizure-like conditions. Remarkably, GqDREADD-mediated activation of wild-type SST interneurons resulted in prolonged electrographic seizures and was accompanied by SST hyperexcitability and depolarization block. Aberrantly large persistent sodium currents, a hallmark of SCN8A mutations, were observed and were found to contribute directly to aberrant SST physiology in computational and pharmacological experiments. These novel findings demonstrate a critical and previously unidentified contribution of SST interneurons to seizure generation not only in SCN8A encephalopathy, but epilepsy in general.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220174,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9474,"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":819338,"name":"Kyle C. A. Wedgwood","orcid":"0000-0002-8109-2765","position":1,"is_corresponding":false},{"id":658663,"name":"Pravin K. Wagley","orcid":"0000-0003-3120-3890","position":2,"is_corresponding":false},{"id":819729,"name":"Samantha M. Strohm","orcid":null,"position":3,"is_corresponding":false},{"id":659370,"name":"Payal S. Panchal","orcid":null,"position":4,"is_corresponding":false},{"id":819730,"name":"Abrar Idrissi Majidi","orcid":null,"position":5,"is_corresponding":false},{"id":658661,"name":"Ian C. Wenker","orcid":"0000-0002-0744-6510","position":6,"is_corresponding":false},{"id":710423,"name":"Ronald P. Gaykema","orcid":"0000-0002-4166-700X","position":7,"is_corresponding":false},{"id":658666,"name":"Manoj K. Patel","orcid":"0000-0003-3591-6716","position":8,"is_corresponding":false},{"id":658662,"name":"Eric R. Wengert","orcid":"0000-0001-7679-4183","position":0,"is_corresponding":true}],"reference_count":68,"raw_metadata":null,"created_at":"2026-07-18T23:53:42.928212Z","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":[]}