{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T05:52:54Z","timestamp":1771566774195,"version":"3.50.1"},"posted":{"date-parts":[[2024,2,15]]},"group-title":"Neuroscience","reference-count":61,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,2,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Hair cells of the inner ear rely on specialized ribbon synapses to transmit sensory information to the central nervous system. The molecules required to assemble these synapses are not fully understood. We show that Nrxn3, a presynaptic adhesion molecule, is critical for ribbon-synapse assembly in hair cells. In both mouse and zebrafish models, loss of Nrxn3 results in significantly fewer intact ribbon synapses. In zebrafish we demonstrate that a 60% loss of synapses in\n                  <jats:italic>nrxn3<\/jats:italic>\n                  mutants dramatically reduces both presynaptic responses in hair cells and postsynaptic responses in afferent neurons. Despite a reduction in synapse function in this model, we find no deficits in the acoustic startle response, a behavior reliant on these synapses. Overall, this work demonstrates that Nrxn3 is a critical and conserved molecule required to assemble ribbon synapses. Understanding how ribbon synapses assemble is a key step towards generating novel therapies to treat forms of age-related and noise-induced hearing loss that occur due to loss of ribbon synapses.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Summary Statement<\/jats:title>\n                  <jats:p>Hearing and balance depend on specialized ribbon synapses that transmit sensory stimuli between hair cells and afferent neurons. We identify Nrxn3 as a key molecular player in ribbon-synapse assembly in hair cells.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2024.02.14.580267","type":"posted-content","created":{"date-parts":[[2024,2,15]],"date-time":"2024-02-15T16:40:10Z","timestamp":1708015210000},"source":"Crossref","is-referenced-by-count":3,"title":["Presynaptic Nrxn3 is essential for ribbon-synapse assembly in hair cells"],"prefix":"10.64898","author":[{"given":"Alma","family":"Jukic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengchang","family":"Lei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-265X","authenticated-orcid":false,"given":"Elizabeth R.","family":"Cebul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine","family":"Pinter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3860-6759","authenticated-orcid":false,"given":"Natalie","family":"Mosqueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandeep","family":"David","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2708-6273","authenticated-orcid":false,"given":"Basile","family":"Tarchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1065-8215","authenticated-orcid":false,"given":"Katie","family":"Kindt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024021703551123000_2024.02.14.580267v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.08.026"},{"key":"2024021703551123000_2024.02.14.580267v1.2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-34-10832.2003"},{"key":"2024021703551123000_2024.02.14.580267v1.3","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0511-18.2018"},{"key":"2024021703551123000_2024.02.14.580267v1.4","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5083-14.2015"},{"key":"2024021703551123000_2024.02.14.580267v1.5","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-022-08971-1"},{"key":"2024021703551123000_2024.02.14.580267v1.6","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1808-15.2016"},{"key":"2024021703551123000_2024.02.14.580267v1.7","doi-asserted-by":"crossref","first-page":"e78649","DOI":"10.7554\/eLife.78649","article-title":"Distinct neurexin-cerebellin complexes control AMPA- and NMDA-receptor responses in a circuit-dependent manner","volume":"11","year":"2022","journal-title":"eLife"},{"key":"2024021703551123000_2024.02.14.580267v1.8","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.33988"},{"key":"2024021703551123000_2024.02.14.580267v1.9","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9549"},{"key":"2024021703551123000_2024.02.14.580267v1.10","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3468-14.2016"},{"key":"2024021703551123000_2024.02.14.580267v1.11","first-page":"1197","article-title":"Hair cell transduction, tuning, and synaptic transmission in the mammalian cochlea","volume":"7","year":"2017","journal-title":"Compr. Physiol"},{"key":"2024021703551123000_2024.02.14.580267v1.12","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4773(01)00382-3"},{"key":"2024021703551123000_2024.02.14.580267v1.13","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19960129)365:1<113::AID-CNE9>3.0.CO;2-6"},{"key":"2024021703551123000_2024.02.14.580267v1.14","doi-asserted-by":"publisher","DOI":"10.1002\/cne.22798"},{"key":"2024021703551123000_2024.02.14.580267v1.15","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24629"},{"key":"2024021703551123000_2024.02.14.580267v1.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2022.04.017"},{"key":"2024021703551123000_2024.02.14.580267v1.17","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1000539"},{"key":"2024021703551123000_2024.02.14.580267v1.18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm247"},{"key":"2024021703551123000_2024.02.14.580267v1.19","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.29275"},{"key":"2024021703551123000_2024.02.14.580267v1.20","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.23661"},{"key":"2024021703551123000_2024.02.14.580267v1.21","doi-asserted-by":"publisher","DOI":"10.1038\/nature11992"},{"key":"2024021703551123000_2024.02.14.580267v1.22","doi-asserted-by":"publisher","DOI":"10.1038\/nature03418"},{"key":"2024021703551123000_2024.02.14.580267v1.23","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.013077"},{"key":"2024021703551123000_2024.02.14.580267v1.24","doi-asserted-by":"publisher","DOI":"10.1002\/dev.420070109"},{"key":"2024021703551123000_2024.02.14.580267v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2009.12.012"},{"key":"2024021703551123000_2024.02.14.580267v1.26","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16113-y"},{"key":"2024021703551123000_2024.02.14.580267v1.27","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm081"},{"key":"2024021703551123000_2024.02.14.580267v1.28","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01108.2011"},{"key":"2024021703551123000_2024.02.14.580267v1.29","doi-asserted-by":"crossref","first-page":"927","DOI":"10.12688\/f1000research.11310.1","article-title":"Noise-induced and age-related hearing loss: new perspectives and potential therapies","volume":"6","year":"2017","journal-title":"F1000Research"},{"key":"2024021703551123000_2024.02.14.580267v1.30","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3389-10.2011"},{"key":"2024021703551123000_2024.02.14.580267v1.31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162726"},{"key":"2024021703551123000_2024.02.14.580267v1.32","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0608536103"},{"key":"2024021703551123000_2024.02.14.580267v1.33","doi-asserted-by":"crossref","unstructured":"Lukasz, D. and Kindt, K. S . (2018). In vivo calcium imaging of lateral-line hair cells in larval zebrafish. J. Vis. Exp. JoVE.","DOI":"10.3791\/58794"},{"key":"2024021703551123000_2024.02.14.580267v1.34","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2019103208"},{"key":"2024021703551123000_2024.02.14.580267v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2016.05.045"},{"key":"2024021703551123000_2024.02.14.580267v1.36","first-page":"633","article-title":"Smaller inner ear sensory epithelia in Neurog 1 null mice are related to earlier hair cell cycle exit","volume":"234","year":"2005","journal-title":"Dev. Dyn. Off. Publ. Am. Assoc. Anat"},{"key":"2024021703551123000_2024.02.14.580267v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nature01755"},{"key":"2024021703551123000_2024.02.14.580267v1.38","doi-asserted-by":"crossref","first-page":"100744","DOI":"10.1016\/j.xpro.2021.100744","article-title":"Fluorescent tagging of endogenous proteins with CRISPR\/Cas9 in primary mouse neural stem cells","volume":"2","year":"2021","journal-title":"STAR Protoc"},{"key":"2024021703551123000_2024.02.14.580267v1.39","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-006-0276-3"},{"key":"2024021703551123000_2024.02.14.580267v1.40","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2425-08.2008"},{"key":"2024021703551123000_2024.02.14.580267v1.41","doi-asserted-by":"crossref","first-page":"e1009937","DOI":"10.1371\/journal.pgen.1009937","article-title":"Neuroplastin genetically interacts with Cadherin 23 and the encoded isoform Np55 is sufficient for cochlear hair cell function and hearing","volume":"18","year":"2022","journal-title":"PLOS Genet"},{"key":"2024021703551123000_2024.02.14.580267v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06033-3"},{"key":"2024021703551123000_2024.02.14.580267v1.43","doi-asserted-by":"crossref","first-page":"104803","DOI":"10.1016\/j.isci.2022.104803","article-title":"Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3","volume":"25","year":"2022","journal-title":"iScience"},{"key":"2024021703551123000_2024.02.14.580267v1.44","doi-asserted-by":"crossref","unstructured":"Schindelin, J. , Arganda-Carreras, I. , Frise, E. , Kaynig, V. , Longair, M. , Pietzsch, T. , Preibisch, S. , Rueden, C. , Saalfeld, S. , Schmid, B ., et al. (2012). Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676\u2013682.","DOI":"10.1038\/nmeth.2019"},{"key":"2024021703551123000_2024.02.14.580267v1.45","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)00159-8"},{"key":"2024021703551123000_2024.02.14.580267v1.46","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1920827118"},{"key":"2024021703551123000_2024.02.14.580267v1.47","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s10162-021-00798-z","article-title":"How zebrafish can drive the future of genetic-based hearing and balance research","volume":"22","year":"2021","journal-title":"JARO J. Assoc. Res. Otolaryngol"},{"key":"2024021703551123000_2024.02.14.580267v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.007"},{"key":"2024021703551123000_2024.02.14.580267v1.49","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0223-04.2004"},{"key":"2024021703551123000_2024.02.14.580267v1.50","doi-asserted-by":"crossref","first-page":"e202103052","DOI":"10.1083\/jcb.202103052","article-title":"The cell biology of synapse formation","volume":"220","year":"2021","journal-title":"J. Cell Biol"},{"key":"2024021703551123000_2024.02.14.580267v1.51","doi-asserted-by":"crossref","unstructured":"Sugita, S. , Saito, F. , Tang, J. , Satz, J. , Campbell, K. and S\u00fcdhof, T. C. (2001). A stoichiometric complex of neurexins and dystroglycan in brain. J. Cell Biol. 154, 435\u2013445.","DOI":"10.1083\/jcb.200105003"},{"key":"2024021703551123000_2024.02.14.580267v1.52","doi-asserted-by":"crossref","unstructured":"Suli, A. , Watson, G. M. , Rubel, E. W. and Raible, D. W . (2012). Rheotaxis in larval zebrafish is mediated by lateral line mechanosensory hair cells. PLoS ONE 7,.","DOI":"10.1371\/journal.pone.0029727"},{"key":"2024021703551123000_2024.02.14.580267v1.53","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.008"},{"key":"2024021703551123000_2024.02.14.580267v1.54","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00574.2004"},{"key":"2024021703551123000_2024.02.14.580267v1.55","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36872-8"},{"key":"2024021703551123000_2024.02.14.580267v1.56","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2022.110624"},{"key":"2024021703551123000_2024.02.14.580267v1.57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.11.025"},{"key":"2024021703551123000_2024.02.14.580267v1.58","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0937-20.2020"},{"key":"2024021703551123000_2024.02.14.580267v1.59","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3238-20.2021"},{"key":"2024021703551123000_2024.02.14.580267v1.60","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3743-14.2015"},{"key":"2024021703551123000_2024.02.14.580267v1.61","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-03806-8"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.02.14.580267","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:57:00Z","timestamp":1768456620000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.02.14.580267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,15]]},"references-count":61,"URL":"https:\/\/doi.org\/10.1101\/2024.02.14.580267","relation":{},"subject":[],"published":{"date-parts":[[2024,2,15]]},"subtype":"preprint"}}