{"oa_version":"Published Version","status":"public","_id":"11143","has_accepted_license":"1","publication":"Cell Reports","volume":38,"license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","abstract":[{"lang":"eng","text":"Dravet syndrome is a neurodevelopmental disorder characterized by epilepsy, intellectual disability, and sudden death due to pathogenic variants in SCN1A with loss of function of the sodium channel subunit Nav1.1. Nav1.1-expressing parvalbumin GABAergic interneurons (PV-INs) from young Scn1a+/− mice show impaired action potential generation. An approach assessing PV-IN function in the same mice at two time points shows impaired spike generation in all Scn1a+/− mice at postnatal days (P) 16–21, whether deceased prior or surviving to P35, with normalization by P35 in surviving mice. However, PV-IN synaptic transmission is dysfunctional in young Scn1a+/− mice that did not survive and in Scn1a+/− mice ≥ P35. Modeling confirms that PV-IN axonal propagation is more sensitive to decreased sodium conductance than spike generation. These results demonstrate dynamic dysfunction in Dravet syndrome: combined abnormalities of PV-IN spike generation and propagation drives early disease severity, while ongoing dysfunction of synaptic transmission contributes to chronic pathology."}],"doi":"10.1016/j.celrep.2022.110580","publication_identifier":{"eissn":["2211-1247"]},"month":"03","isi":1,"acknowledgement":"We would like to thank Bernardo Rudy, Joanna Mattis, and Laura Mcgarry for comments on a previous version of the manuscript; Xiaohong Zhang for expert technical support and mouse colony maintenance; Melody Cheng for assistance with generation of the graphical abstract; and Jennifer Kearney for the gift of Scn1a+/− mice. This work was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under F31NS111803 (to K.M.G.) and K08NS097633 and R01NS110869 (to E.M.G.), the Dravet Syndrome Foundation (to A.S.), an ERC Consolidator Grant (SYNAPSEEK) (to T.P.V.), and the NOMIS Foundation through the NOMIS Fellowships program at IST Austria (to C.C.). The graphical abstract was prepared using BioRender software (BioRender.com).","ddc":["570"],"title":"Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome","day":"29","author":[{"full_name":"Kaneko, Keisuke","last_name":"Kaneko","first_name":"Keisuke"},{"last_name":"Currin","orcid":"0000-0002-4809-5059","full_name":"Currin, Christopher","id":"e8321fc5-3091-11eb-8a53-83f309a11ac9","first_name":"Christopher"},{"first_name":"Kevin M.","full_name":"Goff, Kevin M.","last_name":"Goff"},{"full_name":"Wengert, Eric R.","last_name":"Wengert","first_name":"Eric R."},{"full_name":"Somarowthu, Ala","last_name":"Somarowthu","first_name":"Ala"},{"id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","full_name":"Vogels, Tim P","last_name":"Vogels","orcid":"0000-0003-3295-6181","first_name":"Tim P"},{"full_name":"Goldberg, Ethan M.","last_name":"Goldberg","first_name":"Ethan M."}],"date_created":"2022-04-10T22:01:39Z","intvolume":"        38","scopus_import":"1","file":[{"file_id":"11172","success":1,"creator":"dernst","checksum":"49105c6c27c9af0f37f50a8bbb4d380d","file_name":"2022_CellReports_Kaneko.pdf","content_type":"application/pdf","date_updated":"2022-04-15T11:00:58Z","relation":"main_file","access_level":"open_access","file_size":4774216,"date_created":"2022-04-15T11:00:58Z"}],"citation":{"ama":"Kaneko K, Currin C, Goff KM, et al. Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome. <i>Cell Reports</i>. 2022;38(13). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110580\">10.1016/j.celrep.2022.110580</a>","short":"K. Kaneko, C. Currin, K.M. Goff, E.R. Wengert, A. Somarowthu, T.P. Vogels, E.M. Goldberg, Cell Reports 38 (2022).","ista":"Kaneko K, Currin C, Goff KM, Wengert ER, Somarowthu A, Vogels TP, Goldberg EM. 2022. Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome. Cell Reports. 38(13), 110580.","chicago":"Kaneko, Keisuke, Christopher Currin, Kevin M. Goff, Eric R. Wengert, Ala Somarowthu, Tim P Vogels, and Ethan M. Goldberg. “Developmentally Regulated Impairment of Parvalbumin Interneuron Synaptic Transmission in an Experimental Model of Dravet Syndrome.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110580\">https://doi.org/10.1016/j.celrep.2022.110580</a>.","mla":"Kaneko, Keisuke, et al. “Developmentally Regulated Impairment of Parvalbumin Interneuron Synaptic Transmission in an Experimental Model of Dravet Syndrome.” <i>Cell Reports</i>, vol. 38, no. 13, 110580, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110580\">10.1016/j.celrep.2022.110580</a>.","apa":"Kaneko, K., Currin, C., Goff, K. M., Wengert, E. R., Somarowthu, A., Vogels, T. P., &#38; Goldberg, E. M. (2022). Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110580\">https://doi.org/10.1016/j.celrep.2022.110580</a>","ieee":"K. Kaneko <i>et al.</i>, “Developmentally regulated impairment of parvalbumin interneuron synaptic transmission in an experimental model of Dravet syndrome,” <i>Cell Reports</i>, vol. 38, no. 13. Elsevier, 2022."},"issue":"13","year":"2022","tmp":{"image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)"},"type":"journal_article","ec_funded":1,"article_processing_charge":"No","article_number":"110580","date_updated":"2023-08-03T06:32:55Z","department":[{"_id":"TiVo"}],"publication_status":"published","publisher":"Elsevier","oa":1,"language":[{"iso":"eng"}],"quality_controlled":"1","project":[{"name":"Learning the shape of synaptic plasticity rules for neuronal architectures and function through machine learning.","grant_number":"819603","_id":"0aacfa84-070f-11eb-9043-d7eb2c709234","call_identifier":"H2020"},{"name":"NOMIS Fellowship Program","_id":"9B861AAC-BA93-11EA-9121-9846C619BF3A"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","date_published":"2022-03-29T00:00:00Z","file_date_updated":"2022-04-15T11:00:58Z","external_id":{"isi":["000779794000001"]}}