Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3

Miguel A Ramirez; Yuzuru Ninoyu; Cayla Miller; Leonardo R Andrade; Seby Edassery; Ewa Bomba-Warczak; Briana Ortega; Uri Manor; Mark A Rutherford; Rick A Friedman; Jeffrey N Savas

doi:10.1016/j.isci.2022.104803

Cochlear ribbon synapse maturation requires Nlgn1 and Nlgn3

iScience. 2022 Jul 20;25(8):104803. doi: 10.1016/j.isci.2022.104803. eCollection 2022 Aug 19.

Affiliations

¹ Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
² Division of Otolaryngology, Department of Surgery, University of California, San Diego, 9500 Gilman Drive, Mail Code 0666, La Jolla, CA 92093, USA.
³ Waitt Advanced Biophotonics Core, Salk Institute for Biological Studies, 10010 N. Torrey Pines Road, La Jolla, CA 92037, USA.
⁴ Department of Otolaryngology, Washington University in St. Louis School of Medicine, St. Louis, MO, USA.

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.

Grants and funding

R01 DC014712/DC/NIDCD NIH HHS/United States