{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T21:58:49Z","timestamp":1787003929160,"version":"build-2736575974"},"reference-count":34,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T00:00:00Z","timestamp":1462838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cochlear neuropathy resulting from unsafe noise exposure is a life altering condition that affects many people. This hearing dysfunction follows a conserved mechanism where inner hair cell synapses are lost, termed cochlear synaptopathy. Here we investigate cochlear synaptopathy in the FVB\/nJ mouse strain as a prelude for the investigation of candidate genetic mutations for noise damage susceptibility. We used measurements of auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) to assess hearing recovery in FVB\/nJ mice exposed to two different noise levels. We also utilized confocal fluorescence microscopy in mapped whole mount cochlear tissue, in conjunction with deconvolution and three-dimensional modeling, to analyze numbers, volumes and positions of paired synaptic components. We find evidence for significant synapse reorganization in response to both synaptopathic and sub-synaptopathic noise exposures in FVB\/nJ. Specifically, we find that the modulation in volume of very small synaptic ribbons correlates with the presence of reduced ABR peak one amplitudes in both levels of noise exposures. These experiments define the use of FVB\/nJ mice for further genetic investigations into the mechanisms of noise damage. They further suggest that in the cochlea, neuronal-inner hair cell connections may dynamically reshape as part of the noise response.<\/jats:p>","DOI":"10.1038\/srep25056","type":"journal-article","created":{"date-parts":[[2016,5,10]],"date-time":"2016-05-10T05:44:39Z","timestamp":1462859079000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["Noise exposure modulates cochlear inner hair cell ribbon volumes, correlating with changes in auditory measures in the FVB\/nJ mouse"],"prefix":"10.1038","volume":"6","author":[{"given":"Stephen T.","family":"Paquette","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felicia","family":"Gilels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia M.","family":"White","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,5,10]]},"reference":[{"key":"BFsrep25056_CR1","doi-asserted-by":"publisher","first-page":"13686","DOI":"10.1523\/JNEUROSCI.1783-13.2013","volume":"33","author":"Y Sergeyenko","year":"2013","unstructured":"Sergeyenko, Y., Lall, K., Liberman, M. C. & Kujawa, S. G. Age-related cochlear synaptopathy: an early-onset contributor to auditory functional decline. J Neurosci 33, 13686\u201313694, doi: 10.1523\/JNEUROSCI.1783-13.2013 (2013).","journal-title":"J Neurosci"},{"key":"BFsrep25056_CR2","doi-asserted-by":"publisher","first-page":"1976","DOI":"10.1001\/jama.289.15.1976","volume":"289","author":"B Yueh","year":"2003","unstructured":"Yueh, B., Shapiro, N., MacLean, C. H. & Shekelle, P. G. Screening and management of adult hearing loss in primary care: scientific review. Jama 289, 1976\u20131985, doi: 10.1001\/jama.289.15.1976 (2003).","journal-title":"Jama"},{"key":"BFsrep25056_CR3","first-page":"20","volume":"28","author":"E Stump","year":"2012","unstructured":"Stump, E. A Salute To The Veterans. Hearing Health 28, 20\u201323 (2012).","journal-title":"Hearing Health"},{"key":"BFsrep25056_CR4","unstructured":"Picton, T. W. Human auditory-evoked potentials. (Plural Publishing Inc, 2011)."},{"key":"BFsrep25056_CR5","doi-asserted-by":"publisher","first-page":"14077","DOI":"10.1523\/JNEUROSCI.2845-09.2009","volume":"29","author":"SG Kujawa","year":"2009","unstructured":"Kujawa, S. G. & Liberman, M. C. Adding insult to injury: cochlear nerve degeneration after \u201ctemporary\u201d noise-induced hearing loss. The Journal of neuroscience: the official journal of the Society for Neuroscience 29, 14077\u201314085, doi: 10.1523\/JNEUROSCI.2845-09.2009 (2009).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep25056_CR6","doi-asserted-by":"publisher","first-page":"752","DOI":"10.1177\/000348947608500605","volume":"85","author":"NY Kiang","year":"1976","unstructured":"Kiang, N. Y., Liberman, M. C. & Levine, R. A. Auditory-nerve activity in cats exposed to ototoxic drugs and high-intensity sounds. Ann Otol Rhinol Laryngol 85, 752\u2013768 (1976).","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"BFsrep25056_CR7","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/S0378-5955(99)00003-9","volume":"130","author":"QY Zheng","year":"1999","unstructured":"Zheng, Q. Y., Johnson, K. R. & Erway, L. C. Assessment of hearing in 80 inbred strains of mice by ABR threshold analyses. Hear Res 130, 94\u2013107 (1999).","journal-title":"Hear Res"},{"key":"BFsrep25056_CR8","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1016\/j.heares.2011.11.007","volume":"283","author":"KL Kane","year":"2012","unstructured":"Kane, K. L. et al. Genetic background effects on age-related hearing loss associated with Cdh23 variants in mice. Hear Res 283, 80\u201388, doi: 10.1016\/j.heares.2011.11.007 (2012).","journal-title":"Hear Res"},{"key":"BFsrep25056_CR9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/S0378-5955(99)00210-5","volume":"141","author":"N Yoshida","year":"2000","unstructured":"Yoshida, N., Hequembourg, S. J., Atencio, C. A., Rosowski, J. J. & Liberman, M. C. Acoustic injury in mice: 129\/SvEv is exceptionally resistant to noise-induced hearing loss. Hear Res 141, 97\u2013106 (2000).","journal-title":"Hear Res"},{"key":"BFsrep25056_CR10","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1073\/pnas.88.6.2065","volume":"88","author":"M Taketo","year":"1991","unstructured":"Taketo, M. et al. FVB\/N: an inbred mouse strain preferable for transgenic analyses. Proc Natl Acad Sci U S A 88, 2065\u20132069 (1991).","journal-title":"Proc Natl Acad Sci U S A"},{"key":"BFsrep25056_CR11","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1146\/annurev.genet.35.102401.091224","volume":"35","author":"C Petit","year":"2001","unstructured":"Petit, C., Levilliers, J. & Hardelin, J. P. Molecular genetics of hearing loss. Annual review of genetics 35, 589\u2013646, doi: 10.1146\/annurev.genet.35.102401.091224 (2001).","journal-title":"Annual review of genetics"},{"key":"BFsrep25056_CR12","doi-asserted-by":"crossref","unstructured":"Kommareddi, P. et al. Hair Cell Loss, Spiral Ganglion Degeneration, and Progressive Sensorineural Hearing Loss in Mice with Targeted Deletion of Slc44a2\/Ctl2. J Assoc Res Otolaryngol, doi: 10.1007\/s10162-015-0547-3 (2015).","DOI":"10.1007\/s10162-015-0547-3"},{"key":"BFsrep25056_CR13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1159\/000357770","volume":"4","author":"MK Ho","year":"2014","unstructured":"Ho, M. K., Li, X., Wang, J., Ohmen, J. D. & Friedman, R. A. FVB\/NJ mice demonstrate a youthful sensitivity to noise-induced hearing loss and provide a useful genetic model for the study of neural hearing loss. Audiol Neurotol Extra 4, 1\u201311, doi: 10.1159\/000357770 (2014).","journal-title":"Audiol Neurotol Extra"},{"key":"BFsrep25056_CR14","doi-asserted-by":"publisher","first-page":"7815","DOI":"10.1073\/pnas.82.23.7815","volume":"82","author":"PA Overbeek","year":"1985","unstructured":"Overbeek, P. A., Chepelinsky, A. B., Khillan, J. S., Piatigorsky, J. & Westphal, H. Lens-specific expression and developmental regulation of the bacterial chloramphenicol acetyltransferase gene driven by the murine alpha A-crystallin promoter in transgenic mice. Proc Natl Acad Sci USA 82, 7815\u20137819 (1985).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep25056_CR15","doi-asserted-by":"publisher","first-page":"7293","DOI":"10.1093\/nar\/18.24.7293","volume":"18","author":"T Yokoyama","year":"1990","unstructured":"Yokoyama, T. et al. Conserved cysteine to serine mutation in tyrosinase is responsible for the classical albino mutation in laboratory mice. Nucleic Acids Res 18, 7293\u20137298 (1990).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep25056_CR16","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s11248-006-9056-9","volume":"16","author":"SA Davie","year":"2007","unstructured":"Davie, S. A. et al. Effects of FVB\/NJ and C57Bl\/6 J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice. Transgenic Res 16, 193\u2013201, doi: 10.1007\/s11248-006-9056-9 (2007).","journal-title":"Transgenic Res"},{"key":"BFsrep25056_CR17","doi-asserted-by":"publisher","first-page":"e0124301","DOI":"10.1371\/journal.pone.0124301","volume":"10","author":"H Mutai","year":"2015","unstructured":"Mutai, H., Miya, F., Fujii, M., Tsunoda, T. & Matsunaga, T. Attenuation of progressive hearing loss in DBA\/2 J mice by reagents that affect epigenetic modifications is associated with up-regulation of the zinc importer Zip4. PLos One 10, e0124301, doi: 10.1371\/journal.pone.0124301 (2015).","journal-title":"PLos One"},{"key":"BFsrep25056_CR18","doi-asserted-by":"publisher","first-page":"827","DOI":"10.3109\/00016489109138418","volume":"111","author":"HS Li","year":"1991","unstructured":"Li, H. S. & Borg, E. Age-related loss of auditory sensitivity in two mouse genotypes. Acta Otolaryngol 111, 827\u2013834 (1991).","journal-title":"Acta Otolaryngol"},{"key":"BFsrep25056_CR19","doi-asserted-by":"publisher","first-page":"666","DOI":"10.1002\/cne.903210412","volume":"321","author":"JF Willott","year":"1992","unstructured":"Willott, J. F., Bross, L. S. & McFadden, S. L. Morphology of the dorsal cochlear nucleus in C57BL\/6 J and CBA\/J mice across the life span. J Comp Neurol 321, 666\u2013678, doi: 10.1002\/cne.903210412 (1992).","journal-title":"J Comp Neurol"},{"key":"BFsrep25056_CR20","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/S0378-5955(99)00154-9","volume":"138","author":"AM Jimenez","year":"1999","unstructured":"Jimenez, A. M., Stagner, B. B., Martin, G. K. & Lonsbury-Martin, B. L. Age-related loss of distortion product otoacoustic emissions in four mouse strains. Hear Res 138, 91\u2013105 (1999).","journal-title":"Hear Res"},{"key":"BFsrep25056_CR21","doi-asserted-by":"publisher","first-page":"2115","DOI":"10.1523\/JNEUROSCI.4985-05.2006","volume":"26","author":"SG Kujawa","year":"2006","unstructured":"Kujawa, S. G. & Liberman, M. C. Acceleration of age-related hearing loss by early noise exposure: evidence of a misspent youth. J Neurosci 26, 2115\u20132123, doi: 10.1523\/JNEUROSCI.4985-05.2006 (2006).","journal-title":"J Neurosci"},{"key":"BFsrep25056_CR22","doi-asserted-by":"publisher","first-page":"e0125160","DOI":"10.1371\/journal.pone.0125160","volume":"10","author":"JB Jensen","year":"2015","unstructured":"Jensen, J. B., Lysaght, A. C., Liberman, M. C., Qvortrup, K. & Stankovic, K. M. Immediate and delayed cochlear neuropathy after noise exposure in pubescent mice. PLoS One 10, e0125160, doi: 10.1371\/journal.pone.0125160 (2015).","journal-title":"PLoS One"},{"key":"BFsrep25056_CR23","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1016\/S0378-5955(00)00161-1","volume":"148","author":"N Yoshida","year":"2000","unstructured":"Yoshida, N. & Liberman, M. C. Sound conditioning reduces noise-induced permanent threshold shift in mice. Hear Res 148, 213\u2013219 (2000).","journal-title":"Hear Res"},{"key":"BFsrep25056_CR24","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1152\/jn.00164.2013","volume":"110","author":"AC Furman","year":"2013","unstructured":"Furman, A. C., Kujawa, S. G. & Liberman, M. C. Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates. J Neurophysiol 110, 577\u2013586, doi: 10.1152\/jn.00164.2013 (2013).","journal-title":"J Neurophysiol"},{"key":"BFsrep25056_CR25","doi-asserted-by":"publisher","first-page":"18409","DOI":"10.1523\/JNEUROSCI.2529-13.2013","volume":"33","author":"F Gilels","year":"2013","unstructured":"Gilels, F., Paquette, S. T., Zhang, J., Rahman, I. & White, P. M. Mutation of Foxo3 causes adult onset auditory neuropathy and alters cochlear synapse architecture in mice. The Journal of neuroscience: the official journal of the Society for Neuroscience 33, 18409\u201318424, doi: 10.1523\/JNEUROSCI.2529-13.2013 (2013).","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"key":"BFsrep25056_CR26","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1523\/JNEUROSCI.3389-10.2011","volume":"31","author":"LD Liberman","year":"2011","unstructured":"Liberman, L. D., Wang, H. & Liberman, M. C. Opposing gradients of ribbon size and AMPA receptor expression underlie sensitivity differences among cochlear-nerve\/hair-cell synapses. J Neurosci 31, 801\u2013808, doi: 10.1523\/JNEUROSCI.3389-10.2011 (2011).","journal-title":"J Neurosci"},{"key":"BFsrep25056_CR27","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1007\/s10162-014-0462-z","volume":"15","author":"Y Yin","year":"2014","unstructured":"Yin, Y., Liberman, L. D., Maison, S. F. & Liberman, M. C. Olivocochlear innervation maintains the normal modiolar-pillar and habenular-cuticular gradients in cochlear synaptic morphology. J Assoc Res Otolaryngol 15, 571\u2013583, doi: 10.1007\/s10162-014-0462-z (2014).","journal-title":"J Assoc Res Otolaryngol"},{"key":"BFsrep25056_CR28","doi-asserted-by":"publisher","first-page":"7509","DOI":"10.1523\/JNEUROSCI.5138-14.2015","volume":"35","author":"KA Fernandez","year":"2015","unstructured":"Fernandez, K. A., Jeffers, P. W., Lall, K., Liberman, M. C. & Kujawa, S. G. Aging after noise exposure: acceleration of cochlear synaptopathy in \u201crecovered\u201d ears. J Neurosci 35, 7509\u20137520, doi: 10.1523\/JNEUROSCI.5138-14.2015 (2015).","journal-title":"J Neurosci"},{"key":"BFsrep25056_CR29","doi-asserted-by":"crossref","unstructured":"Kujawa, S. G. & Liberman, M. C. Synaptopathy in the noise-exposed and aging cochlea: Primary neural degeneration in acquired sensorineural hearing loss. Hear Res, doi: 10.1016\/j.heares.2015.02.009 (2015).","DOI":"10.1016\/j.heares.2015.02.009"},{"key":"BFsrep25056_CR30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/S0196-0709(79)80004-6","volume":"1","author":"WC Stebbins","year":"1979","unstructured":"Stebbins, W. C., Hawkins, J. E., Jr., Johnson, L. G. & Moody, D. B. Hearing thresholds with outer and inner hair cell loss. Am J Otolaryngol 1, 15\u201327 (1979).","journal-title":"Am J Otolaryngol"},{"key":"BFsrep25056_CR31","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1121\/1.401307","volume":"90","author":"JC Saunders","year":"1991","unstructured":"Saunders, J. C., Cohen, Y. E. & Szymko, Y. M. The structural and functional consequences of acoustic injury in the cochlea and peripheral auditory system: a five year update. J Acoust Soc Am 90, 136\u2013146 (1991).","journal-title":"J Acoust Soc Am"},{"key":"BFsrep25056_CR32","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1016\/0378-5955(80)90007-6","volume":"3","author":"MC Liberman","year":"1980","unstructured":"Liberman, M. C. Morphological differences among radial afferent fibers in the cat cochlea: an electron-microscopic study of serial sections. Hear Res 3, 45\u201363 (1980).","journal-title":"Hear Res"},{"key":"BFsrep25056_CR33","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/1471-2105-10-145","volume":"10","author":"K Lo","year":"2009","unstructured":"Lo, K., Hahne, F., Brinkman, R. R. & Gottardo, R. flowClust: a Bioconductor package for automated gating of flow cytometry data. BMC bioinformatics 10, 145, doi: 10.1186\/1471-2105-10-145 (2009).","journal-title":"BMC bioinformatics"},{"key":"BFsrep25056_CR34","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1002\/cyto.a.20531","volume":"73","author":"K Lo","year":"2008","unstructured":"Lo, K., Brinkman, R. R. & Gottardo, R. Automated gating of flow cytometry data via robust model-based clustering. Cytometry A 73, 321\u2013332, doi: 10.1002\/cyto.a.20531 (2008).","journal-title":"Cytometry A"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep25056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep25056","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep25056.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T23:05:33Z","timestamp":1672873533000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep25056"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,10]]},"references-count":34,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,5,31]]}},"alternative-id":["BFsrep25056"],"URL":"https:\/\/doi.org\/10.1038\/srep25056","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,10]]},"assertion":[{"value":"14 January 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 April 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25056"}}