{"doi":"10.1101/2021.07.28.454042","title":"Developmentally-regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome","abstract":"ABSTRACT Dravet syndrome (DS) is a neurodevelopmental disorder defined by epilepsy, intellectual disability, and sudden death, due to heterozygous variants in SCN1A with loss of function of the sodium channel subunit Nav1.1. Nav1.1-expressing parvalbumin GABAergic interneurons (PV-INs) from pre-weanling Scn1a+/− mice show impaired action potential generation. A novel approach assessing PV-IN function in the same mice at two developmental time points showed that, at post-natal day (P) 16-21, spike generation was impaired all mice, deceased prior or surviving to P35. However, synaptic transmission was selectively dysfunctional in pre-weanling mice that did not survive. Spike generation in surviving mice normalized by P35, yet we again identified abnormalities in synaptic transmission. We conclude that combined dysfunction of PV-IN spike generation and synaptic transmission drives disease severity, while ongoing dysfunction of synaptic transmission contributes to chronic pathology. Modeling revealed that PV-IN axonal propagation is more sensitive to decreases in sodium conductance than spike generation.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":217699,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9607,"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":814651,"name":"Christopher Brian Currin","orcid":"0000-0002-4809-5059","position":1,"is_corresponding":false},{"id":284609,"name":"Kevin M. Goff","orcid":"0000-0001-5862-0219","position":2,"is_corresponding":false},{"id":284608,"name":"Ala Somarowthu","orcid":"0000-0001-8109-3816","position":3,"is_corresponding":false},{"id":814652,"name":"Tim P. Vogels","orcid":"0000-0003-3295-6181","position":4,"is_corresponding":false},{"id":227207,"name":"Ethan M. Goldberg","orcid":"0000-0002-7404-735X","position":5,"is_corresponding":false},{"id":811206,"name":"Keisuke Kaneko","orcid":"0000-0002-5071-0057","position":0,"is_corresponding":true}],"reference_count":78,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:20.374789Z","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":[]}