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To further characterize hair cell synaptic elements in myo7aa\u2212\/\u2212 mutants, we focused on the ribbon synapse and evaluated ultrastructure, number and distribution of immunolabeled ribbons, and postsynaptic densities. By transmission electron microscopy, we determined that myo7aa\u2212\/\u2212 zebrafish have fewer glutamatergic vesicles tethered to ribbon synapses, yet maintain a comparable ribbon area. In myo7aa\u2212\/\u2212 hair cells, immunolocalization of Ctbp2 showed fewer ribbon-containing cells in total and an altered distribution of Ctbp2 puncta compared to wild-type hair cells. myo7aa\u2212\/\u2212 mutants have fewer postsynaptic densities \u2013 as assessed by MAGUK immunolabeling \u2013 compared to wild-type zebrafish. We quantified the circular swimming behavior of myo7aa\u2212\/\u2212 mutant fish and measured a greater turning angle (absolute smooth orientation). It has previously been shown that L-type voltage-gated calcium channels are necessary for ribbon localization and occurrence of postsynaptic density; thus, we hypothesized and observed that L-type voltage-gated calcium channel agonists change behavioral and synaptic phenotypes in myo7aa\u2212\/\u2212 mutants in a drug-specific manner. Our results indicate that treatment with L-type voltage-gated calcium channel agonists alter hair cell synaptic elements and improve behavioral phenotypes of myo7aa\u2212\/\u2212 mutants. Our data support that L-type voltage-gated calcium channel agonists induce morphological changes at the ribbon synapse \u2013 in both the number of tethered vesicles and regarding the distribution of Ctbp2 puncta \u2013 shift swimming behavior and improve acoustic startle response.<\/jats:p>","DOI":"10.1242\/dmm.043885","type":"journal-article","created":{"date-parts":[[2020,11,27]],"date-time":"2020-11-27T15:15:11Z","timestamp":1606490111000},"source":"Crossref","is-referenced-by-count":9,"title":["L-type voltage-gated calcium channel agonists mitigate hearing loss and modify ribbon synapse morphology in the zebrafish model of Usher syndrome type 1"],"prefix":"10.1242","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7949-7205","authenticated-orcid":false,"given":"Alaa","family":"Koleilat","sequence":"first","affiliation":[{"name":"College of Continuing and Professional Studies 1 , , Minneapolis, MN 55108 , USA"},{"name":"University of Minnesota 1 , , Minneapolis, MN 55108 , USA"},{"name":"2 Mayo Clinic Graduate School of Biomedical Sciences, Clinical and Translational Science Track, Rochester, MN 55905, USA"},{"name":"Center for Clinical and Translational Science 3 , Mayo Clinic, Rochester, MN 55905 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph A.","family":"Dugdale","sequence":"additional","affiliation":[{"name":"4 Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Trace A.","family":"Christenson","sequence":"additional","affiliation":[{"name":"Mayo Clinic Microscopy and Cell Analysis Core 5 , Rochester, MN 55905 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey L.","family":"Bellah","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Science 3 , Mayo Clinic, Rochester, MN 55905 , USA"},{"name":"Columbia University 6 Department of Genetics and Development , , New York City, NY 10032 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron M.","family":"Lambert","sequence":"additional","affiliation":[{"name":"University of Minnesota 7 Department of Neuroscience , , Minneapolis, MN 55455 , USA"},{"name":"Harvard University 8 Department of Molecular and Cellular Biology , , Cambridge, MA 02138 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark A.","family":"Masino","sequence":"additional","affiliation":[{"name":"University of Minnesota 7 Department of Neuroscience , , Minneapolis, MN 55455 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0726-4212","authenticated-orcid":false,"given":"Stephen C.","family":"Ekker","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Science 3 , Mayo Clinic, Rochester, MN 55905 , USA"},{"name":"9 Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3154-4249","authenticated-orcid":false,"given":"Lisa A.","family":"Schimmenti","sequence":"additional","affiliation":[{"name":"4 Department of Otorhinolaryngology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"9 Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA"},{"name":"University of Minnesota 10 Department of Pediatrics , , Minneapolis, MN 55455 , USA"},{"name":"University of Minnesota 11 Department of Genetics, Cell Biology and Development , , Minneapolis, MN 55455 , USA"},{"name":"University of Minnesota 12 Department of Ophthalmology and Visual Neuroscience , , Minneapolis, MN 55454 , USA"},{"name":"13 Department of Clinical Genomics, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2020,11,27]]},"reference":[{"key":"2024061302334738900_DMM043885C1","doi-asserted-by":"publisher","first-page":"7022","DOI":"10.1523\/JNEUROSCI.1163-06.2006","article-title":"The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15","volume":"26","author":"Ahmed","year":"2006","journal-title":"J. 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