@article{132379bee4a047ce991cfeb45466cdcf,
title = "Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3",
abstract = "Hearing depends on precise synaptic transmission between cochlear inner hair cells and spiral ganglion neurons through afferent ribbon synapses. Neuroligins (Nlgns) facilitate synapse maturation in the brain, but they have gone unstudied in the cochlea. We report Nlgn3 and Nlgn1 knockout (KO) cochleae have fewer ribbon synapses and have impaired hearing. Nlgn3 KO is more vulnerable to noise trauma with limited activity at high frequencies one day after noise. Furthermore, Nlgn3 KO cochleae have a 5-fold reduction in synapse number compared to wild type after two weeks of recovery. Double KO cochlear phenotypes are more prominent than the KOs, for example, 5-fold smaller synapses, 25% reduction in synapse density, and 30% less synaptic output. These observations indicate Nlgn3 and Nlgn1 are essential to cochlear ribbon synapse maturation and function.",
keywords = "cellular neuroscience, genomics, neuroscience, sensory neuroscience",
author = "Ramirez, {Miguel A.} and Yuzuru Ninoyu and Cayla Miller and Andrade, {Leonardo R.} and Seby Edassery and Ewa Bomba-Warczak and Briana Ortega and Uri Manor and Rutherford, {Mark A.} and Friedman, {Rick A.} and Savas, {Jeffrey N.}",
note = "Funding Information: We thank Joris De Wit, Jaime Garcia-A{\~n}overos, Nopporn Jongkamonwiwat, Anis Contractor, and members of the Savas laboratory for insightful discussions. We would also like to thank Nils Brose for generously sharing Nlgn1 and Nlgn3 KO mice for this study and John Reynolds for the marmoset tissue. Some of the image analysis in this article was derived from the Northwestern University Center for Advanced Molecular Imaging, which is generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center. This work was supported by T32 MH067564 to M.A.R1. 5R01 DC018566 to R.A.F. R01 DC014712 to M.A.R.2, R00 DC-013805, W81XWH-19-1-0627, an NU Knowles Hearing Center Pilot award to J.N.S. U.M. is supported by the Chan-Zuckerberg Initiative Imaging Scientist Award, NSF NeuroNex Award No. 2014862, R21 DC018237, the Greenwall Foundation. The Waitt Advanced Biophotonics Core is supported by NIH-NCI CCSG: P30 014195. M.A.R1. M.A.R2. U.M. R.A.F, and J.N.S designed the experiments. M.A.R1. performed nearly all the experiments and S.E. participated in the proteomic analysis. Y.U. and B.O. analyzed GWAS data and performed some IF and ABRs for the cKO mice, C.M. quantified some IF. L.R.A. performed and quantified the TEM. M.A.R1. M.A.R2. and J.N.S. wrote the article. The authors declare no competing interests. Funding Information: We thank Joris De Wit, Jaime Garcia-A{\~n}overos, Nopporn Jongkamonwiwat, Anis Contractor, and members of the Savas laboratory for insightful discussions. We would also like to thank Nils Brose for generously sharing Nlgn1 and Nlgn3 KO mice for this study and John Reynolds for the marmoset tissue. Some of the image analysis in this article was derived from the Northwestern University Center for Advanced Molecular Imaging, which is generously supported by NCI CCSG P30 CA060553 awarded to the Robert H Lurie Comprehensive Cancer Center . This work was supported by T32 MH067564 to M.A.R 1 ., 5R01 DC018566 to R.A.F., R01 DC014712 to M.A.R. 2 , R00 DC-013805 , W81XWH-19-1-0627 , an NU Knowles Hearing Center Pilot award to J.N.S.. U.M. is supported by the Chan-Zuckerberg Initiative Imaging Scientist Award, NSF NeuroNex Award No. 2014862 , R21 DC018237 , the Greenwall Foundation . The Waitt Advanced Biophotonics Core is supported by NIH -NCI CCSG: P30 014195 . Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = aug,
day = "19",
doi = "10.1016/j.isci.2022.104803",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
number = "8",
}