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Genet"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"451","DOI":"10.3109\/00016486509124579","article-title":"Development of hearing in the normal CBA-J mouse: correlation of physiological observations with behavioral responses and with cochlear anatomy","volume":"59","author":"D Mikaelian","year":"1965","journal-title":"Acta Otolaryngol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1113\/jphysiol.1951.sp004655","article-title":"A theory of the effects of fibre size in medullated nerve","volume":"115","author":"W Rushton","year":"1951","journal-title":"Journal of Physiology"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"14078","DOI":"10.1523\/JNEUROSCI.3765-07.2007","article-title":"Auditory neurons make stereotyped wiring decisions before maturation of their targets","volume":"27","author":"EJ Koundakjian","year":"2007","journal-title":"Journal of 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Boca Raton: CRC Press LLC. pp. 37\u201358."},{"key":"ref37","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1007\/s10162-013-0419-7","article-title":"Ouabain-induced cochlear nerve degeneration: synaptic loss and plasticity in a mouse model of auditory neuropathy","volume":"15","author":"Y Yuan","year":"2014","journal-title":"JARO"},{"key":"ref38","first-page":"179","article-title":"Development of absolute auditory thresholds in the house mouse (<italic>Mus musculus<\/italic>)","volume":"1","author":"G Ehret","year":"1976","journal-title":"J Am Audiol Soc"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"14288","DOI":"10.1074\/jbc.C500024200","article-title":"A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for disproportionate dwarfism in cn\/cn mouse","volume":"280","author":"T Tsuji","year":"2005","journal-title":"Journal of Biological 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Neurophysiol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1152\/jn.1998.79.1.51","article-title":"Synaptic inputs to stellate cells in the ventral cochlear nucleus","volume":"79","author":"MJ Ferragamo","year":"1998","journal-title":"J Neurophysiol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1523\/JNEUROSCI.04-06-01577.1984","article-title":"Intracellular injection with horseradish peroxidase of physiologically characterized stellate and bushy cells in slices of mouse anteroventral cochlear nucleus","volume":"4","author":"SH Wu","year":"1984","journal-title":"Journal of Neuroscience"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/(SICI)1096-9861(19970825)385:2<245::AID-CNE5>3.0.CO;2-1","article-title":"Projections from the ventral cochlear nucleus to the dorsal cochlear nucleus in rats","volume":"385","author":"JR Doucet","year":"1997","journal-title":"J Comp 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