{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T23:12:48Z","timestamp":1790205168718,"version":"4.1.0"},"reference-count":69,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,1,4]],"date-time":"2018-01-04T00:00:00Z","timestamp":1515024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["DC013841"],"award-info":[{"award-number":["DC013841"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>Auditory brainstem neurons of all vertebrates fire phase\u2010locked action potentials (APs) at high rates with remarkable fidelity, a process controlled by specialized anatomical and biophysical properties.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This is especially true in the avian nucleus magnocellularis (NM) \u2013 the analogue of the mammalian anteroventral cochlear nucleus.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>In addition to high voltage\u2010activated potassium (K<jats:sub>HVA<\/jats:sub>) channels, we report, using whole cell physiology and modelling, that resurgent sodium current (<jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub>) of sodium channels (Na<jats:sub>V<\/jats:sub>) is equally important and operates synergistically with K<jats:sub>HVA<\/jats:sub> channels to enable rapid AP firing in NM.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Anatomically, we detected strong Na<jats:sub>V<\/jats:sub>1.6 expression near hearing maturation, which was less distinct during hearing development despite functional evidence of <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub>, suggesting that multiple Na<jats:sub>V<\/jats:sub> channel subtypes may contribute to <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub>.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>We conclude that <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>Auditory brainstem neurons are functionally primed to fire action potentials (APs) at markedly high rates in order to rapidly encode the acoustic information of sound. This specialization is critical for survival and the comprehension of behaviourally relevant communication functions, including sound localization and distinguishing speech from noise. Here, we investigated underlying ion channel mechanisms essential for high\u2010rate AP firing in neurons of the chicken nucleus magnocellularis (NM) \u2013 the avian analogue of bushy cells of the mammalian anteroventral cochlear nucleus. In addition to the established function of high voltage\u2010activated potassium channels, we found that resurgent sodium current (<jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub>) plays a role in regulating rapid firing activity of late\u2010developing (embryonic (E) days 19\u201321) NM neurons. <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> of late\u2010developing NM neurons showed similar properties to mammalian neurons in that its unique mechanism of an \u2018open channel block state\u2019 facilitated the recovery and increased the availability of sodium (Na<jats:sub>V<\/jats:sub>) channels after depolarization. Using a computational model of NM neurons, we demonstrated that removal of <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> reduced high\u2010rate AP firing. We found weak <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> during a prehearing period (E11\u201312), which transformed to resemble late\u2010developing <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> properties around hearing onset (E14\u201316). Anatomically, we detected strong Na<jats:sub>V<\/jats:sub>1.6 expression near maturation, which became increasingly less distinct at hearing onset and prehearing periods, suggesting that multiple Na<jats:sub>V<\/jats:sub> channel subtypes may contribute to <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> during development. We conclude that <jats:italic>I<\/jats:italic><jats:sub>NaR<\/jats:sub> plays an important role in regulating rapid AP firing for NM neurons, a property that may be evolutionarily conserved for functions related to similar avian and mammalian hearing.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp275083","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T17:25:51Z","timestamp":1511976351000},"page":"423-443","source":"Crossref","is-referenced-by-count":16,"title":["Resurgent sodium current promotes action potential firing in the avian auditory brainstem"],"prefix":"10.1113","volume":"596","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2963-3771","authenticated-orcid":false,"given":"Hui","family":"Hong","sequence":"first","affiliation":[{"name":"Roxelyn and Richard Pepper Department of Communication Sciences and Disorders Northwestern University  Evanston IL 60208 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Florida State University  Tallahassee FL 32306 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0115-846X","authenticated-orcid":false,"given":"Jason Tait","family":"Sanchez","sequence":"additional","affiliation":[{"name":"Roxelyn and Richard Pepper Department of Communication Sciences and Disorders Northwestern University  Evanston IL 60208 USA"},{"name":"Department of Neurobiology Northwestern University  Evanston IL 60208 USA"},{"name":"The Hugh Knowles Hearing Research Center Northwestern University  Evanston IL 60208 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