Three-dimensional structure of inner ear hair cell mitochondrial networks and ribbon synapses in a zebrafish model of Usher syndrome type 1B

Inner ear hair cells are the fundamental unit of sound and vibration detection in inner ear and lateral line structures. Our understanding of the structure and ultrastructure of hair cells has heretofore relied upon two-dimensional imaging. The development of serial block-face scanning electron microscopy (SBFSEM) changes this paradigm and allows for ultrastructural evaluation of hair cells in three-dimensions. This is the first report of SBFSEM analysis in the myo7aa-/- mutant where we evaluated several attributes of zebrafish hair cells from the inner ear cristae in both wildtype and myo7aa-/- mutant zebrafish through three-dimensional reconstruction. We describe ribbon synapse number, location, and volume, mitochondrial localization, and innervation for individual hair cells. We determined that myo7aa-/- mutant ribbon synapses have a smaller volume and surface area; however, all other hair cell attributes investigated were not significantly different between the mutant and wildtype zebrafish. These findings are critical for the development of therapies for deafness caused by mutations in myo7aa, as this study supports that the necessary hair cell machinery for hearing is largely intact. In addition, the methodology and measurements developed in this study provide a guide for the evaluation of zebrafish hair cells using SBFSEM.