scholarly journals Coordinated calcium signalling in cochlear sensory and non‐sensory cells refines afferent innervation of outer hair cells

2019 ◽  
Vol 38 (9) ◽  
Author(s):  
Federico Ceriani ◽  
Aenea Hendry ◽  
Jing‐Yi Jeng ◽  
Stuart L Johnson ◽  
Friederike Stephani ◽  
...  
Keyword(s):  
Hair Cells ◽  
Calcium Signalling ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Afferent Innervation

scholarly journals Spontaneous and coordinated Ca2+ activity of cochlear sensory and non-sensory cells drives the maturation of OHC afferent innervation

2018 ◽  
Author(s):  
Federico Ceriani ◽  
Aenea Hendry ◽  
Jing-Yi Jeng ◽  
Stuart L. Johnson ◽  
Jennifer Olt ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Outer Hair Cells ◽  
Fine Tuning ◽  
Sensory Cells ◽  
Early Postnatal Development ◽  
Acoustic Stimuli ◽  
Ribbon Synapses ◽  
Immature Development ◽  
Afferent Innervation

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca2+ signalling in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca2+ signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca2+ spikes during a narrow period of immature development. Simultaneously, waves of Ca2+ activity in the non-sensory greater epithelial ridge act, via ATP-induced activation of P2X receptors, to synchronize OHC firing, resulting in the refinement of their afferent innervation. In the absence of connexin channels Ca2+ waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity in OHCs requires experience-independent Ca2+ signals from sensory and non-sensory cells.

Outer Hair Cells Provide Active Tuning in the Organ of Corti

Physiology ◽  
1998 ◽  
Vol 13 (3) ◽  
pp. 107-111 ◽  
Author(s):  
Mats Ulfendahl ◽  
Åke Flock
Keyword(s):  
Mechanical Behavior ◽  
Hair Cells ◽  
Organ Of Corti ◽  
High Sensitivity ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Effector Cells ◽  
Hearing Organ

The detection of sound by the mammalian hearing organ, the organ of Corti, is far from a passive process with the sensory cells acting as mere receptors. The high sensitivity and sharp tuning of the auditory apparatus are very much dependant on the active mechanical behavior of the outer hair cells, acting as effector cells.

scholarly journals Sensory Transduction and Adaptation in Inner and Outer Hair Cells of the Mouse Auditory System

2007 ◽  
Vol 98 (6) ◽  
pp. 3360-3369 ◽  
Author(s):  
Eric A. Stauffer ◽  
Jeffrey R. Holt
Keyword(s):  
Hair Cells ◽  
Slow Component ◽  
Outer Hair Cells ◽  
Fast Component ◽  
Sensory Transduction ◽  
Hair Bundle ◽  
Sensory Cells ◽  
Auditory Hair Cells ◽  
Inner Hair Cells ◽  
The Difference

Auditory function in the mammalian inner ear is optimized by collaboration of two classes of sensory cells known as inner and outer hair cells. Outer hair cells amplify and tune sound stimuli that are transduced and transmitted by inner hair cells. Although they subserve distinct functions, they share a number of common properties. Here we compare the properties of mechanotransduction and adaptation recorded from inner and outer hair cells of the postnatal mouse cochlea. Rapid outer hair bundle deflections of about 0.5 micron evoked average maximal transduction currents of about 325 pA, whereas inner hair bundle deflections of about 0.9 micron were required to evoke average maximal currents of about 310 pA. The similar amplitude was surprising given the difference in the number of stereocilia, 81 for outer hair cells and 48 for inner hair cells, but may be reconciled by the difference in single-channel conductance. Step deflections of inner and outer hair bundles evoked adaptation that had two components: a fast component that consisted of about 60% of the response occurred over the first few milliseconds and a slow component that consisted of about 40% of the response followed over the subsequent 20–50 ms. The rate of the slow component in both inner and outer hair cells was similar to the rate of slow adaptation in vestibular hair cells. The rate of the fast component was similar to that of auditory hair cells in other organisms and several properties were consistent with a model that proposes calcium-dependent release of tension allows transduction channel closure.

scholarly journals Scanning Electron Microscopy of the Human Organ of Corti

1983 ◽  
Vol 76 (4) ◽  
pp. 269-278 ◽  
Author(s):  
A Wright
Keyword(s):  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Surface Appearance ◽  
Human Organ ◽  
Human Cochlea ◽  
Temporal Bones ◽  
Subsequent Staining ◽  
Scanning Electron

The human cochlea has been preserved from post-mortem autolysis by perfusion with a fixative shortly after death. Subsequent staining with osmium permits dissection of this structure from the temporal bone. (Temporal bones were obtained from eight patients). When prepared for examination in the scanning electron microscope, the auditory sensory cells are found to be located in the band-like organ of Corti which extends the length of the cochlea. The sensory cells have a cluster of stereocilia projecting from their free upper surface and because of this are called hair cells. The hair cells are divided into two separate groups: a single row of inner hair cells, which show little variation in their surface appearance along the length of the cochlea, and three or four rows of outer hair cells whose cilia change in conformation and increase in length along the cochlea.

scholarly journals Hair Cell Generation in Cochlear Culture Models Mediated by Novel γ-Secretase Inhibitors

2021 ◽  
Vol 9 ◽  
Author(s):  
Silvia T. Erni ◽  
John C. Gill ◽  
Carlotta Palaferri ◽  
Gabriella Fernandes ◽  
Michelle Buri ◽  
...  
Keyword(s):  
Hair Cell ◽  
Notch Signaling ◽  
Hair Cells ◽  
Round Window ◽  
Notch Pathway ◽  
Outer Hair Cells ◽  
Round Window Membrane ◽  
Sensory Cells ◽  
Supporting Cells

Sensorineural hearing loss is prevalent within society affecting the quality of life of 460 million worldwide. In the majority of cases, this is due to insult or degeneration of mechanosensory hair cells in the cochlea. In adult mammals, hair cell loss is irreversible as sensory cells are not replaced spontaneously. Genetic inhibition of Notch signaling had been shown to induce hair cell formation by transdifferentiation of supporting cells in young postnatal rodents and provided an impetus for targeting Notch pathway with small molecule inhibitors for hearing restoration. Here, the oto-regenerative potential of different γ-secretase inhibitors (GSIs) was evaluated in complementary assay models, including cell lines, organotypic cultures of the organ of Corti and cochlear organoids to characterize two novel GSIs (CPD3 and CPD8). GSI-treatment induced hair cell gene expression in all these models and was effective in increasing hair cell numbers, in particular outer hair cells, both in baseline conditions and in response to ototoxic damage. Hair cells were generated from transdifferentiation of supporting cells. Similar findings were obtained in cochlear organoid cultures, used for the first time to probe regeneration following sisomicin-induced damage. Finally, effective absorption of a novel GSI through the round window membrane and hair cell induction was attained in a whole cochlea culture model and in vivo pharmacokinetic comparisons of transtympanic delivery of GSIs and different vehicle formulations were successfully conducted in guinea pigs. This preclinical evaluation of targeting Notch signaling with novel GSIs illustrates methods of characterization for hearing restoration molecules, enabling translation to more complex animal studies and clinical research.

scholarly journals Quantitative Fluorescent in situ Hybridization Reveals Differential Transcription Profile Sharpening of Endocytic Proteins in Cochlear Hair Cells Upon Maturation

2021 ◽  
Vol 15 ◽  
Author(s):  
Guobin Huang ◽  
Stephanie Eckrich
Keyword(s):  
Hair Cells ◽  
Outer Hair Cells ◽  
Sensory Cells ◽  
Vesicle Membrane ◽  
Cochlear Hair Cells ◽  
Transcription Profiles ◽  
Whole Mount ◽  
Differential Transcription ◽  
Endocytic Proteins

The organ of Corti (OC) comprises two types of sensory cells: outer hair cells (OHCs) and inner hair cells (IHCs). While both are mechanotransducers, OHCs serve as cochlear amplifiers, whereas IHCs transform sound into transmitter release. Reliable sound encoding is ensured by indefatigable exocytosis of synaptic vesicles associated with efficient replenishment of the vesicle pool. Vesicle reformation requires retrieval of vesicle membrane from the hair cell’s membrane via endocytosis. So far, the protein machinery for endocytosis in pre-mature and terminally differentiated hair cells has only partially been deciphered. Here, we studied three endocytic proteins, dynamin-1, dynamin-3, and endophilin-A1, by assessing their transcription profiles in pre-mature and mature mouse OCs. State-of-the-art RNAscope® fluorescent in situ hybridization (FISH) of whole-mount OCs was used for quantification of target mRNAs on single-cell level. We found that pre-mature IHCs contained more mRNA transcripts of dnm1 (encoding dynamin-1) and sh3gl2 (endophilin-A1), but less of dnm3 (dynamin-3) than OHCs. These differential transcription profiles between OHCs and IHCs were sharpened upon maturation. It is noteworthy that low but heterogeneous signal numbers were found between individual negative controls, which highlights the importance of corresponding analyses in RNAscope® assays. Complementary immunolabeling revealed strong expression of dynamin-1 in the soma of mature IHCs, which was much weaker in pre-mature IHCs. By contrast, dynamin-3 was predominantly found in the soma and at the border of the cuticular plates of pre-mature and mature OHCs. In summary, using quantitative RNAscope® FISH and immunohistochemistry on whole-mount tissue of both pre-mature and mature OCs, we disclosed the cellular upregulation of endocytic proteins at the level of transcription/translation during terminal differentiation of the OC. Dynamin-1 and endophilin-A1 likely contribute to the strengthening of the endocytic machinery in IHCs after the onset of hearing, whereas expression of dynamin-3 at the cuticular plate of pre-mature and mature OHCs suggests its possible involvement in activity-independent apical endocytosis.

scholarly journals Membrane Electromechanics in Biology, with a Focus on Hearing

MRS Bulletin ◽  
2009 ◽  
Vol 34 (9) ◽  
pp. 665-670 ◽  
Author(s):  
F. Sachs ◽  
W. E. Brownell ◽  
A. G. Petrov
Keyword(s):  
Hair Cells ◽  
Material Properties ◽  
High Speed ◽  
Thermal Noise ◽  
Electrical Energy ◽  
Outer Hair Cells ◽  
Frequency Resolution ◽  
Sensory Cells ◽  
Energy Store ◽  
Internal Potential

AbstractCells are ion conductive gels surrounded by a ∼5-nm-thick insulating membrane, and molecular ionic pumps in the membrane establish an internal potential of approximately −90 mV. This electrical energy store is used for high-speed communication in nerve and muscle and other cells. Nature also has used this electric field for high-speed motor activity, most notably in the ear, where transduction and detection can function as high as 120 kHz. In the ear, there are two sets of sensory cells: the “inner hair cells” that generate an electrical output to the nervous system and the more numerous “outer hair cells” that use electromotility to counteract viscosity and thus sharpen resonance to improve frequency resolution. Nature, in a remarkable exhibition of nanomechanics, has made out of soft, aqueous materials a microphone and high-speed decoder capable of functioning at 120 kHz, limited only by thermal noise. Both physics and biology are only now becoming aware of the material properties of biomembranes and their ability to perform work and sense the environment. We anticipate new examples of this biopiezoelectricity will be forthcoming.

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