Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets

Development ◽  
1995 ◽  
Vol 121 (10) ◽  
pp. 3381-3391 ◽  
Author(s):  
T. Schimmang ◽  
L. Minichiello ◽  
E. Vazquez ◽  
I. San Jose ◽  
F. Giraldez ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Catalytic Domain ◽  
Sensory System ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Developmental Study ◽  
Inner Hair Cells ◽  
Vestibular Neurons ◽  
Cochlear Neurons

The trkB and trkC genes are expressed during the formation of the vestibular and auditory system. To elucidate the function of trkB and trkC during this process, we have analysed mice carrying a germline mutation in the tyrosine kinase catalytic domain of these genes. Neuroanatomical analysis of homozygous mutant mice revealed neuronal deficiencies in the vestibular and cochlear ganglia. In trkB (−/−) animals vestibular neurons and a subset of cochlear neurons responsible for the innervation of outer hair cells were drastically reduced. The peripheral targets of the respective neurons showed severe innervation defects. A comparative analysis of ganglia from trkC (−/−) mutants revealed a moderate reduction of vestibular neurons and a specific loss of cochlear neurons innervating inner hair cells. No nerve fibres were detected in the sensory epithelium containing inner hair cells. A developmental study of trkB (−/−) and trkC (−/−) mice showed that some vestibular and cochlear fibres initially reached their peripheral targets but failed to maintain innervation and degenerated. TrkB and TrkC receptors are therefore required for the survival of specific neuronal populations and the maintenance of target innervation in the peripheral sensory system of the inner ear.

Ionic Currents and Electromotility in Inner Ear Hair Cells From Humans

1998 ◽  
Vol 79 (4) ◽  
pp. 2235-2239 ◽  
Author(s):  
John S. Oghalai ◽  
Jeffrey R. Holt ◽  
Takashi Nakagawa ◽  
Thomas M. Jung ◽  
Newton J. Coker ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Ionic Currents ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Sensory Receptor ◽  
Surgical Removal ◽  
Type I ◽  
Vestibular Hair Cells ◽  
Sensory Receptor Cells

Oghalai, John S., Jeffrey R. Holt, Takashi Nakagawa, Thomas M. Jung, Newton J. Coker, Herman A. Jenkins, Ruth Anne Eatock, and William E. Brownell. Ionic currents and electromotility in inner ear hair cells from humans. J. Neurophysiol. 79: 2235–2239, 1998. The upright posture and rich vocalizations of primates place demands on their senses of balance and hearing that differ from those of other animals. There is a wealth of behavioral, psychophysical, and CNS measures characterizing these senses in primates, but no prior recordings from their inner ear sensory receptor cells. We harvested human hair cells from patients undergoing surgical removal of life-threatening brain stem tumors and measured their ionic currents and electromotile responses. The hair cells were either isolated or left in situ in their sensory epithelium and investigated using the tight-seal, whole cell technique. We recorded from both type I and type II vestibular hair cells under voltage clamp and found four voltage-dependent currents, each of which has been reported in hair cells of other animals. Cochlear outer hair cells demonstrated electromotility in response to voltage steps like that seen in rodent animal models. Our results reveal many qualitative similarities to hair cells obtained from other animals and justify continued investigations to explore quantitative differences that may be associated with normal or pathological human sensation.

scholarly journals Aquaporin-6 Expression in the Cochlear Sensory Epithelium Is Downregulated by Salicylates

2010 ◽  
Vol 2010 ◽  
pp. 1-8 ◽  
Author(s):  
Paola Perin ◽  
Simona Tritto ◽  
Laura Botta ◽  
Jacopo Maria Fontana ◽  
Giulia Gastaldi ◽  
...  
Keyword(s):  
Inner Ear ◽  
Expression Pattern ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Rt Pcr ◽  
Supporting Cells ◽  
Sensory Epithelia ◽  
Mechanical Compliance

We characterize the expression pattern of aquaporin-6 in the mouse inner ear by RT-PCR and immunohistochemistry. Our data show that in the inner ear aquaporin-6 is expressed, in both vestibular and acoustic sensory epithelia, by the supporting cells directly contacting hair cells. In particular, in the Organ of Corti, expression was strongest in Deiters' cells, which provide both a mechanical link between outer hair cells (OHCs) and the Organ of Corti, and an entry point for ion recycle pathways. Since aquaporin-6 is permeable to both water and anions, these results suggest its possible involvement in regulating OHC motility, directly through modulation of water and chloride flow or by changing mechanical compliance in Deiters' cells. In further support of this role, treating mice with salicylates, which impair OHC electromotility, dramatically reduced aquaporin-6 expression in the inner ear epithelia but not in control tissues, suggesting a role for this protein in modulating OHCs' responses.

scholarly journals Static length changes of cochlear outer hair cells can tune low-frequency hearing

2017 ◽  
Author(s):  
Nikola Ciganović ◽  
Rebecca L. Warren ◽  
Batu Keçeli ◽  
Stefan Jacob ◽  
Anders Fridberger ◽  
...  
Keyword(s):  
Inner Ear ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Outer Hair Cells ◽  
Frequency Selectivity ◽  
Apical Region ◽  
Low Frequencies ◽  
Inner Hair Cells ◽  
Length Changes ◽  
The Brain

AbstractThe cochlea not only transduces sound-induced vibration into neural spikes, it also amplifies weak sound to boost its detection. Actuators of this active process are sensory outer hair cells in the organ of Corti, whereas the inner hair cells transduce the resulting motion into electric signals that propagate via the auditory nerve to the brain. However, how the outer hair cells modulate the stimulus to the inner hair cells remains unclear. Here, we combine theoretical modeling and experimental measurements near the cochlear apex to study the way in which length changes of the outer hair cells deform the organ of Corti. We develop a geometry-based kinematic model of the apical organ of Corti that reproduces salient, yet counter-intuitive features of the organ’s motion. Our analysis further uncovers a mechanism by which a static length change of the outer hair cells can sensitively tune the signal transmitted to the sensory inner hair cells. When the outer hair cells are in an elongated state, stimulation of inner hair cells is largely inhibited, whereas outer hair cell contraction leads to a substantial enhancement of sound-evoked motion near the hair bundles. This novel mechanism for regulating the sensitivity of the hearing organ applies to the low frequencies that are most important for the perception of speech and music. We suggest that the proposed mechanism might underlie frequency discrimination at low auditory frequencies, as well as our ability to selectively attend auditory signals in noisy surroundings.Author summaryOuter hair cells are highly specialized force producers inside the inner ear: they can change length when stimulated electrically. However, how exactly this electromotile effect contributes to the astonishing sensitivity and frequency selectivity of the inner ear has remained unclear. Here we show for the first time that static length changes of outer hair cells can sensitively regulate how much of a sound signal is passed on to the inner hair cells that forward the signal to the brain. Our analysis holds for the apical region of the inner ear that is responsible for detecting the low frequencies that matter most in speech and music. This shows a mechanisms for how frequency-selectivity can be achieved at low frequencies. It also opens a path for the efferent neural system to regulate hearing sensitivity.

The developing organ of Corti contains retinoic acid and forms supernumerary hair cells in response to exogenous retinoic acid in culture

Development ◽  
1993 ◽  
Vol 119 (4) ◽  
pp. 1041-1053 ◽  
Author(s):  
M.W. Kelley ◽  
X.M. Xu ◽  
M.A. Wagner ◽  
M.E. Warchol ◽  
J.T. Corwin
Keyword(s):  
Retinoic Acid ◽  
Hair Cells ◽  
Organ Of Corti ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Supporting Cells ◽  
Embryonic Mouse ◽  
Inner Hair Cells ◽  
Sensory Epithelia

The mammalian organ of Corti has one of the most highly ordered patterns of cells in any vertebrate sensory epithelium. A single row of inner hair cells and three or four rows of outer hair cells extend along its length. The factors that regulate the formation of this strict pattern are unknown. In order to determine whether retinoic acid plays a role during the development of the organ of Corti, exogenous retinoic acid was added to embryonic mouse cochleae in vitro. Exogenous retinoic acid significantly increased the number of cells that developed as hair cells and resulted in large regions of supernumerary hair cells and supporting cells containing two rows of inner hair cells and up to 11 rows of outer hair cells. The effects of retinoic acid were dependent on concentration and on the timing of its addition. Western blot analysis indicated that cellular retinoic acid binding protein (CRABP) was present in the sensory epithelium of the embryonic cochlea. The amount of CRABP apparently increased between embryonic day 14 and postnatal day 1, but CRABP was not detectable in sensory epithelia from adults. A retinoic acid reporter cell line was used to demonstrate that retinoic acid was also present in the developing organ of Corti between embryonic day 14 and postnatal day 1, and was also present in adult cochleae at least in the vicinity of the modiolus. These results suggest that retinoic acid is involved in the normal development of the organ of Corti and that the effect of retinoic acid may be to induce a population of prosensory cells to become competent to differentiate as hair cells and supporting cells.

scholarly journals Optimization of spectral-domain optical coherence tomography with a supercontinuum source for in vivo motion detection of low reflective outer hair cells in guinea pig cochleae

2021 ◽  
Author(s):  
Fumiaki Nin ◽  
Samuel Choi ◽  
Takeru Ota ◽  
Zhang Qi ◽  
Hiroshi Hibino
Keyword(s):  
Optical Coherence Tomography ◽  
High Resolution ◽  
Guinea Pig ◽  
Hair Cells ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Acquisition Time ◽  
Total Acquisition Time ◽  
Sd Oct

AbstractSound evokes sub-nanoscale vibration within the sensory epithelium. The epithelium contains not only immotile cells but also contractile outer hair cells (OHCs) that actively shrink and elongate synchronously with the sound. However, the in vivo motion of OHCs has remained undetermined. The aim of this work is to perform high-resolution and -accuracy vibrometry in live guinea pigs with an SC-introduced spectral-domain optical coherence tomography system (SD-OCT). In this study, to reveal the effective contribution of SC source in the recording of the low reflective materials with the short total acquisition time, we compare the performances of the SC-introduced SD-OCT (SCSD-OCT) to that of the conventional SD-OCT. As inanimate comparison objects, we record a mirror, a piezo actuator, and glass windows. For the measurements in biological materials, we use in/ex vivo guinea pig cochleae. Our study achieved the optimization of a SD-OCT system for high-resolution in vivo vibrometry in the cochlear sensory epithelium, termed the organ of Corti, in mammalian cochlea. By introducing a supercontinuum (SC) light source and reducing the total acquisition time, we improve the axial resolution and overcome the difficulty in recording the low reflective material in the presence of biological noise. The high power of the SC source enables the system to achieve a spatial resolution of 1.72 ± 0.00 μm on a mirror and reducing the total acquisition time contributes to the high spatial accuracy of sub-nanoscale vibrometry. Our findings reveal the vibrations at the apical/basal region of OHCs and the extracellular matrix, basilar membrane.

Hes1 is a negative regulator of inner ear hair cell differentiation

Development ◽  
2000 ◽  
Vol 127 (21) ◽  
pp. 4551-4560 ◽  
Author(s):  
J.L. Zheng ◽  
J. Shou ◽  
F. Guillemot ◽  
R. Kageyama ◽  
W.Q. Gao
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Inner Ear ◽  
Cell Fate ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Negative Regulator ◽  
Pcr Analysis ◽  
Loss Of Function ◽  
Hair Cell Differentiation

Hair cell fate determination in the inner ear has been shown to be controlled by specific genes. Recent loss-of-function and gain-of-function experiments have demonstrated that Math1, a mouse homolog of the Drosophila gene atonal, is essential for the production of hair cells. To identify genes that may interact with Math1 and inhibit hair cell differentiation, we have focused on Hes1, a mammalian hairy and enhancer of split homolog, which is a negative regulator of neurogenesis. We report here that targeted deletion of Hes1 leads to formation of supernumerary hair cells in the cochlea and utricle of the inner ear. RT-PCR analysis shows that Hes1 is expressed in inner ear during hair cell differentiation and its expression is maintained in adulthood. In situ hybridization with late embryonic inner ear tissue reveals that Hes1 is expressed in supporting cells, but not hair cells, of the vestibular sensory epithelium. In the cochlea, Hes1 is selectively expressed in the greater epithelial ridge and lesser epithelial ridge regions which are adjacent to inner and outer hair cells. Co-transfection experiments in postnatal rat explant cultures show that overexpression of Hes1 prevents hair cell differentiation induced by Math1. Therefore Hes1 can negatively regulate hair cell differentiation by antagonizing Math1. These results suggest that a balance between Math1 and negative regulators such as Hes1 is crucial for the production of an appropriate number of inner ear hair cells.

High-Voltage Electron Microscopic Study of the Inner Ear: Technique and Preliminary Results

1983 ◽  
Vol 92 (1_suppl) ◽  
pp. 3-12 ◽  
Author(s):  
Tomonori Takasaka ◽  
Hideich Shinkawa ◽  
Kozo Watanuki ◽  
Sho Hashimoto ◽  
Kazutomo Kawamoto
Keyword(s):  
Electron Microscopy ◽  
Hair Cell ◽  
Inner Ear ◽  
High Voltage ◽  
Hair Cells ◽  
Outer Hair Cells ◽  
Tectorial Membrane ◽  
Preliminary Results ◽  
Voltage Electron ◽  
Cuticular Plate

The technique and some preliminary results of the application of high-voltage electron microscopy (HVEM) to the study of inner ear morphology in the guinea pig are reported in this paper. The main advantage of HVEM is that sharp images of thicker specimens can be obtained because of the greater penetrating power of high energy electrons. The optimum thickness of the sections examined with an accelerating voltage of 1,000 kV was found to be between 500 to 800 nm. The sections below 500 nm in thickness often had insufficient contrast, while those above 800 nm were rather difficult to interpret due to overlap of images of the organelles. The whole structure of the sensory hairs from the tip to the rootlet was more frequently observed in the 800-nm thick sections. Thus the fine details of the hair attachment to the tectorial membrane as well as the hair rootlet extension into the cuticular plate could be thoroughly studied in the HVEM. In specimens fixed in aldehyde containing 2% tannic acid, the attachment of the tips of the outer hair cell stereocilia to the tectorial membrane was observed. For the inner hair cells, however, the tips of the hairs were separated from the undersurface of the tectorial membrane. The majority of the rootlets of the outer hair cells terminated at the midportion of the cuticular plate, while most of the inner hair cell rootlets traversed the entire width of the cuticular plate and extended into the apical cytoplasm. These differences in ultrastructural appearance may indicate that the two kinds of hair cells play different roles in the acoustic transduction process. The three-dimensional arrangement of the nerve endings on the hair cells was also studied by the serial thick-sectioning technique in the HVEM. In general, an entire arrangement of the nerve endings was almost completely cut in less than ten 800-nm thick sections instead of the 50- to 100-ultrathin (ie, less than 100 nm) conventional sections for transmission electron microscopy. The present study confirms an earlier report that the first row outer hair cells in the third cochlear turn are innervated by nearly equal numbers of efferent and afferent endings, the average number being nine.

scholarly journals Author Correction: Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1

Nature ◽  
2018 ◽  
Vol 565 (7737) ◽  
pp. E2-E2
Author(s):  
Teerawat Wiwatpanit ◽  
Sarah M. Lorenzen ◽  
Jorge A. Cantú ◽  
Chuan Zhi Foo ◽  
Ann K. Hogan ◽  
...  
Keyword(s):  
Hair Cells ◽  
Outer Hair Cells ◽  
Inner Hair Cells

scholarly journals A counter gradient of Activin A and follistatin instructs the timing of hair cell differentiation in the murine cochlea

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Meenakshi Prajapati-DiNubila ◽  
Ana Benito-Gonzalez ◽  
Erin Jennifer Golden ◽  
Shuran Zhang ◽  
Angelika Doetzlhofer
Keyword(s):  
Cell Differentiation ◽  
Hair Cell ◽  
Hair Cells ◽  
Activin A ◽  
Sensory Epithelium ◽  
Outer Hair Cells ◽  
Longitudinal Gradient ◽  
Hair Cell Differentiation ◽  
Local Gradient ◽  
Molecular Signals

The mammalian auditory sensory epithelium has one of the most stereotyped cellular patterns known in vertebrates. Mechano-sensory hair cells are arranged in precise rows, with one row of inner and three rows of outer hair cells spanning the length of the spiral-shaped sensory epithelium. Aiding such precise cellular patterning, differentiation of the auditory sensory epithelium is precisely timed and follows a steep longitudinal gradient. The molecular signals that promote auditory sensory differentiation and instruct its graded pattern are largely unknown. Here, we identify Activin A and its antagonist follistatin as key regulators of hair cell differentiation and show, using mouse genetic approaches, that a local gradient of Activin A signaling within the auditory sensory epithelium times the longitudinal gradient of hair cell differentiation. Furthermore, we provide evidence that Activin-type signaling regulates a radial gradient of terminal mitosis within the auditory sensory epithelium, which constitutes a novel mechanism for limiting the number of inner hair cells being produced.

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