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Ramirez, Miguel A.; Ninoyu, Yuzuru; Miller, Cayla; Andrade, Leonardo R.; Edassery, Seby; Bomba-Warczak, Ewa; Ortega, Briana; Manor, Uri; Rutherford, Mark A.; Friedman, Rick A.; Savas, Jeffrey N.
iScience, 08/2022, Letnik: 25, Številka: 8Journal Article
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. Display omitted •Nlgn3 is a major synapse organizing protein in spiral ganglion neurons•Nlgn1 and three KO cochlea have reduced ribbon synapse density and hampered function•Nlgn3 KO mice are highly sensitive to noise exposures•dKO cochlear phenotypes are generally synergistic and severe Genomics; Neuroscience; Cellular neuroscience; Sensory neuroscience
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