Hair cell synaptic ribbons are essential for synchronous auditory signalling

Darina Khimich; Régis Nouvian; Rémy Pujol; Susanne tom Dieck; Alexander Egner; Eckart D. Gundelfinger; Tobias Moser

doi:10.1038/nature03418

Ribeye a-mCherry fusion protein: A novel tool for labeling synaptic ribbons of the hair cell

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2010.11.011 ◽

2011 ◽

Vol 197 (2) ◽

pp. 274-278 ◽

Cited By ~ 4

Author(s):

Megan C. West ◽

Brian M. McDermott

Keyword(s):

Fusion Protein ◽

Hair Cell ◽

Protein A ◽

Synaptic Ribbons

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Otoferlin Depletion Results in Abnormal Synaptic Ribbons and Altered Intracellular Calcium Levels in Zebrafish

Scientific Reports ◽

10.1038/s41598-019-50710-2 ◽

2019 ◽

Vol 9 (1) ◽

Author(s):

Aayushi Manchanda ◽

Paroma Chatterjee ◽

Josephine A. Bonventre ◽

Derik E. Haggard ◽

Katie S. Kindt ◽

...

Keyword(s):

Hair Cell ◽

Synaptic Vesicle ◽

Hair Cells ◽

Calcium Binding ◽

Synaptic Ribbons ◽

Vesicle Recycling ◽

Synaptic Vesicle Exocytosis ◽

Expression Of Genes ◽

Vesicle Exocytosis ◽

The Impact

Abstract The protein otoferlin plays an essential role at the sensory hair cell synapse. Mutations in otoferlin result in deafness and depending on the species, mild to strong vestibular deficits. While studies in mouse models suggest a role for otoferlin in synaptic vesicle exocytosis and endocytosis, it is unclear whether these functions are conserved across species. To address this question, we characterized the impact of otoferlin depletion in zebrafish larvae and found defects in synaptic vesicle recycling, abnormal synaptic ribbons, and higher resting calcium concentrations in hair cells. We also observed abnormal expression of the calcium binding hair cell genes s100s and parvalbumin, as well as the nogo related proteins rtn4rl2a and rtn4rl2b. Exogenous otoferlin partially restored expression of genes affected by endogenous otoferlin depletion. Our results suggest that in addition to vesicle recycling, depletion of otoferlin disrupts resting calcium levels, alters synaptic ribbon architecture, and perturbs transcription of hair cells specific genes during zebrafish development.

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Treatment with Piribedil and Memantine Reduces Noise-Induced Loss of Inner Hair Cell Synaptic Ribbons

Scientific Reports ◽

10.1038/srep30821 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 9

Author(s):

Richard A. Altschuler ◽

Noel Wys ◽

Diane Prieskorn ◽

Cathy Martin ◽

Susan DeRemer ◽

...

Keyword(s):

Hair Cell ◽

Synaptic Ribbons ◽

Inner Hair Cell

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Histological evaluation of cochlear hair cell damage from noise-induced hearing loss in chinchillas

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100159217 ◽

1990 ◽

Vol 48 (3) ◽

pp. 332-333

Author(s):

R.V. Harrison ◽

R.J. Mount ◽

P. White ◽

N. Fukushima

Keyword(s):

Hair Cell ◽

Evoked Potential ◽

Cell Damage ◽

Acoustic Trauma ◽

Histological Evaluation ◽

Cell Integrity ◽

Functional Changes ◽

Cochlear Hair Cell ◽

Left And Right ◽

Contralateral Ear

In studies which attempt to define the influence of various factors on recovery of hair cell integrity after acoustic trauma, an experimental and a control ear which initially have equal degrees of damage are required. With in a group of animals receiving an identical level of acoustic trauma there is more symmetry between the ears of each individual, in respect to function, than between animals. Figure 1 illustrates this, left and right cochlear evoked potential (CAP) audiograms are shown for two chinchillas receiving identical trauma. For this reason the contralateral ear is used as control.To compliment such functional evaluations we have devised a scoring system, based on the condition of hair cell stereocilia as revealed by scanning electron microscopy, which permits total stereociliar damage to be expressed numerically. This quantification permits correlation of the degree of structural pathology with functional changes. In this paper wereport experiments to verify the symmetry of stereociliar integrity between two ears, both for normal (non-exposed) animals and chinchillas in which each ear has received identical noise trauma.

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The Organization of Actin Filaments in the Stereocilia of the Bird Cochlea

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s1431927600002452 ◽

1980 ◽

Vol 38 ◽

pp. 554-555

Author(s):

E.J. Battles ◽

D. DeRosier ◽

J.C. Saunders ◽

L.G. Tilney

Keyword(s):

Hair Cell ◽

Diffraction Pattern ◽

Sea Urchin ◽

Actin Filaments ◽

Optical Diffraction ◽

Dense Material ◽

Apical Surface ◽

Structural Rigidity ◽

High Degree ◽

Degree Of Order

Extending from the apical surface of each hair cell of the chick cochlea are from 75 to 200 microvilli or stereocllia and one true cllium, the kinocilium. The stereocllia are arranged in rows of progressively increasing length (Fig. 1). Within each tapering sterocilium is a bundle of actin filaments with over 900 filaments near the tip yet only approximately 25 at the base where filaments are enmeshed in a dense material (Fig. 1); from here some of the filaments enter the apical surface of the cell (cuticular plate) as a rootlet. Examination of longitudinal sections of the stereocilia (Fig. 2) show that the filaments are aligned parallel to each other and show considerable order. Examination of an optical diffraction pattern of this bundle (Fig. 4) reveal that the actin filaments are packed such that the crossover points of adjacent actin filaments are inregister. A prominent reflection at 125Å−1 demonstrates that the filaments are cjossbridged by a macromolecular bridge situated at an average of 125Å−1 intervals (Fig. 4) in transverse sections the filaments appear hexagonally packed although there are regions where the filaments are less ordered (Fig. 3). In images processed in the computer to remove, noise and enhance detail periodic nature of the bridge can be clearly seen (see arrows Fig. 5). This image resembles that of an actin paracrystal formed from sea urchin extract composed of bundles of actin filaments crossbridged by a second protein. Thus the actin filaments in the bird stereocilia by being cross-bridged and packed with a high degree of order and produces a structure with considerable structural rigidity. Embryos were studied at various stages in development in an attempt to determine how the stereocilia form and how does the actin packing develops. These stages will be discussed.

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