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PubMed1997

Cellular interactions as a response to injury in the organ of Corti in culture.

We discovered and described ultrastructurally the intricate relationships between the sensory cells and their supporting cells in cultures of the organ of Corti following laser beam irradiation. Injury was performed using a 440 nm nitrogen-dye pulse laser aimed at the cuticular plates of inner hair cells. Laser injury is compared with mechanical injury inflicted on the hair cell region by a pulled-glass pipette. Regardless of the type of injury, but depending on its severity, the surviving hair cells may: (1) lose their stereocilia but subsist at the surface of the organ; (2) retain contact with the reticular lamina but be overgrown by the processes of the supporting cells; or (3) become sequestered from the reticular lamina and internalized among the supporting cells, where they either remain dedifferentiated or regrow an apical process which regains contact with the surface of the organ. All supporting cells, including pillar and Deiters cells take part in wrapping their respective inner or outer hair cells. The supporting cells not only cover the injured sensory cells, but also invert their villi toward the maimed cuticular plates and release an extracellular matrix around them. We suggest that the supporting cells play a protective and trophic role in the recovery of injured hair cells.

Animals↗
PubMed1998

The generation of DC potentials in a computational model of the organ of Corti: effects of voltage-dependent K+ channels in the basolateral membrane of the inner hair cell.

A computational model of the organ of Corti is described to assist in the interpretation of electrophysiological data concerning the role of the K+ channels residing in the basolateral membrane of cochlear hair cells. Recent in vivo data from Van Emst et al. (Hear. Res. 88, 27-35 (1995); Hear. Res. 102, 70-80 (1996)) about the effects of selective blocking of K+ channels indicate that these channels affect the magnitude of the summating potential. In order to understand the nature of this effect, the model of Dallos (Hear. Res. 14, 281-291 (1984)) was extended to account for the voltage- and time-dependent properties of the K+ channels in the basolateral membrane of the inner hair cell (IHC) (Kros and Crawford, J. Physiol. 421, 262-291 (1990)). The model shows that the K+ channels induce a shift in the mean IHC basolateral conductance when high-frequency stimuli are present. As a result, cochlear transduction shifts to a different electrical operating state and this is the source of a marked decrease in the stimulus-evoked DC response of the IHC. Extracellularly, in contrast, the magnitude of the DC response increases slightly. At low frequencies, the K+ channels respond to the stimulus waveform on a cycle-by-cycle basis. The waveform distortion associated with this dynamic basolateral impedance induces a further decrease in the intracellular stimulus-evoked DC response of the IHC. Thus, K+ channels in the IHC appear to be directly involved in the generation of the DC receptor potential at low frequencies, but at high frequencies they simply modify the size of the DC response.

Acoustic Stimulation↗
PubMed1990

Does electrical stimulation of the crossed olivo-cochlear bundle produce movement of the organ of Corti?

Low-frequency microphonic waveforms have been recorded in the basal turn of the guinea pig cochlea with and without electrical stimulation of the crossed olivocochlear bundle (COCB) at the floor of the fourth ventricle. Stimulation of the COCB increased the amplitude of the microphonic waveforms as described previously, but did not alter the shape of the waveforms markedly. The changes observed with COCB stimulation are consistent with a reduction in the impedance of the basolateral wall of the outer hair cells by about 50%, and possibly a 20% increase in the vibration of the organ of Corti at low frequencies, but suggest little or no change in the operating point on the transfer curve relating deflection of the hair bundles to the receptor current through the hair cells. It therefore seems that if slow contraction of the outer hair cells occurs during acute efferent stimulation in vivo, then it produces only a small deflection of the outer hair cell stereocilia, equivalent to a transverse displacement of the organ of Corti of less than 1.5 nm.

Action Potentials↗
PubMed1993

E-cadherin in the mature and developing organ of Corti of the mouse.

The reticular lamina of the mammalian cochlea is formed by the tightly joined apical surfaces of hair cells and supporting cells. This lamina creates a barrier separating endolymph and perilymph, two fluids of different composition. The preservation of this fluid barrier is a requirement of cochlear function. This study aimed to determine whether the calcium-dependent, cell adhesion molecule, E-cadherin was appropriately placed both temporally and spatially to contribute to the formation and maintenance of the reticular lamina. Cochleas aged E15 to P31 were stained immunocytochemically for E-cadherin. In the P31 organ of Corti, E-cadherin is localized to the apical intercellular junctions of supporting cells, but is absent from supporting cell-hair cell borders. During development, E-cadherin is present only on the apices and lateral edges of those cells which will eventually lie adjacent to fluid spaces--pillar, outer hair and Deiters cells. The molecule disappears from the lateral cell membranes at about the time in development that fluid spaces form. These data suggest that E-cadherin plays a role in maintaining the reticular lamina by mediating inter-supporting cell adhesion and raise the possibility that fluid space opening in the organ of Corti is facilitated by the down-regulation or redistribution of E-cadherin.

Animals↗
PubMedDate not supplied

Electrophysiological monitoring of the cochlea during and after total destruction of the organ of corti.

A series of acoustically evoked potentials can be recorded from the cochlea up to the auditory cortex in guinea pigs where the organ of Corti has been totally destroyed after extensive treatment with amikacin, but where some of the spiral ganglion neurons always remain and where the vestibular receptors are only slightly affected. The cochlear responses have been monitored in guinea pigs permanently implanted with a round window electrode and receiving such treatment. The normal auditory nerve compound action potential disappears within a few days, while the very typical response (diphasic, short latency (0.3 ms) small amplitude) appears. This response then remains remarkably constant in time as far as we could observe (up to almost one year). This response might be a component of the normal response, undiscernible under normal conditions but revealed by the selective impairment of the labyrinth by amikacin, in contrast to the global effect of every other known otodestructive agent. Some basic questions still remain: which fibres are effectively stimulated (cochlear or vestibular), what are their central projections, and what kind of sensation is conceivably associated with these responses?

Amikacin↗
PubMed1993

The innervation of the organ of Corti in the rat.

To date our knowledge of the baso-apical distribution of the afferent and efferent nerve fibers innervating the organ of Corti is only fragmentary. This study makes an effort to lay the basis for a comprehensive analysis of cochlear innervation. Using a quantitative electronmicroscopic method, the fiber density of all cochlear fibers along the entire length of the cochlear duct was investigated in adult rats, Rattus norvegicus. Myelinated and unmyelinated nerve fibers in the primary osseous spiral lamina and afferent and efferent nerve fibers to the outer hair cells (OHCs) in the tunnel of Corti were counted. The rat cochlea is innervated by 19000 nerve fibers which consist of 79% afferent and 21% efferent fibers. The inner hair cells (IHCs) are innervated by 14000 afferent and 2000 efferent fibers. The OHCs are innervated by 1000 afferent and 2000 efferent fibers. The maximum fiber density of IHC afferents, OHC afferents and IHC efferents was found in the middle of the cochlea. This corresponds to the region at the basilar membrane where the frequency range of maximum sensitivity is located [8 kHz-31 kHz; Kelly and Masterton, J. Comp. Physiol. Psychol. 91, 930-936 (1977)]. The efferent nerve fibers to the OHCs consists of two different morphological sub-types: large fibers containing mitochondria and neurotubules (type I) and small fibers containing neurofilaments (type II). The fiber density of type I OHC efferents decreases from base to apex corresponding to the frequency dispersion along the basilar membrane. The fiber density of type II OHC efferents has maxima at the base and at the apex and a minimum in the middle of the cochlea. This minimum corresponds to the region at the basilar membrane where the frequency range of maximum sensitivity is located.

Animals↗
PubMed1990

Investigation of intracellular organelles in the human organ of Corti using backscattered electrons (BSE).

Using ligand-mediated osmification (OTOTO technique), human cochleae were prepared for scanning electron microscopy. The surface of the organ of Corti and the bodies of the sensory cells were observed with secondary and backscattered electrons. Detecting the backscattered electrons emitted from the depth of the cells, intracellular organelles such as subsurface cisternae, mitochondria and nuclei became visible in their reciprocal arrangement.

Histological Techniques↗
PubMed2006

A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development.

The molecular mechanisms coordinating cell cycle exit with cell differentiation and organogenesis are a crucial, yet poorly understood, aspect of normal development. The mammalian cyclin-dependent kinase inhibitor p27(Kip1) is required for the correct timing of cell cycle exit in developing tissues, and thus plays a crucial role in this process. Although studies of p27(Kip1) regulation have revealed important posttranscriptional mechanisms regulating p27(Kip1) abundance, little is known about how developmental patterns of p27(Kip1) expression, and thus cell cycle exit, are achieved. Here, we show that during inner ear development transcriptional regulation of p27(Kip1) is the primary determinant of a wave of cell cycle exit that dictates the number of postmitotic progenitors destined to give rise to the hair cells and supporting cells of the organ of Corti. Interestingly, transcriptional induction from the p27(Kip1) gene occurs normally in p27(Kip1)-null mice, indicating that developmental regulation of p27(Kip1) transcription is independent of the timing of cell cycle exit. In addition, cell-type-specific patterns of p27(Kip1) transcriptional regulation are observed in the mature organ of Corti and retina, suggesting that this mechanism is important in differential regulation of the postmitotic state. This report establishes a link between the spatial and temporal pattern of p27(Kip1) transcription and the control of cell number during sensory organ morphogenesis.

Animals↗
PubMed1980

Method for tracing single fibers in the organ of Corti with horseradish peroxidase.

A method based on the axonal transport of horseradish peroxidase (HRP) has been developed to trace single fibers in the organ of Corti. HRP was injected into the auditory nerve or cochlear nucleus of the adult chinchilla, and the entire cochlea was subsequently incubated for reaction product. Of most significance was the Golgi-like labelling of single radial afferents innervating the inner hair cells. Heretofore, radial afferents have been difficult to trace with more conventional staining techniques, especially in adult animals. Outer spiral fibers, presumably afferent, were also labelled in one of the cochleas.

Animals↗
PubMed2006

Engraftment and differentiation of embryonic stem cell-derived neural progenitor cells in the cochlear nerve trunk: growth of processes into the organ of Corti.

Hearing loss in mammals is irreversible because cochlear neurons and hair cells do not regenerate. To determine whether we could replace neurons lost to primary neuronal degeneration, we injected EYFP-expressing embryonic stem cell-derived mouse neural progenitor cells into the cochlear nerve trunk in immunosuppressed animals 1 week after destroying the cochlear nerve (spiral ganglion) cells while leaving hair cells intact by ouabain application to the round window at the base of the cochlea in gerbils. At 3 days post transplantation, small grafts were seen that expressed endogenous EYFP and could be immunolabeled for neuron-specific markers. Twelve days after transplantation, the grafts had neurons that extended processes from the nerve core toward the denervated organ of Corti. By 64-98 days, the grafts had sent out abundant processes that occupied a significant portion of the space formerly occupied by the cochlear nerve. The neurites grew in fasciculating bundles projecting through Rosenthal's canal, the former site of spiral ganglion cells, into the osseous spiral lamina and ultimately into the organ of Corti, where they contacted hair cells. Neuronal counts showed a significant increase in neuronal processes near the sensory epithelium, compared to animals that were denervated without subsequent stem cell transplantation. The regeneration of these neurons shows that neurons differentiated from stem cells have the capacity to grow to a specific target in an animal model of neuronal degeneration.

Animals↗
PubMedDate not supplied

Nerve fibers in the fetal organ of Corti. Scanning electron microscopic study.

Four human fetal inner ears ranging from 22 to 25 weeks' gestation were examined by scanning electron microscopy. Dissection of the organ of Corti revealed nerve fibers at the bottom of Corti's tunnel and the first row of the external spiral bundles on the medial wall of Deiters' cells. The nerve fiber arrangement was more complicated compared to that of animals so far reported. Thin nerve fibers which ran irregularly and showed branching were found both in Corti's tunnel and in the external spiral bundle and at times were connected to the tunnel medial fibers. These thin fibers were estimated to be efferent in nature.

Gestational Age↗
PubMed1992

[Fine structure of the guinea pig organ of Corti revealed by a quick-freeze, freeze-substitution method].

A quick-freeze, freeze-substitution method was applied to the guinea pig organ of Corti. Many similarities were apparent between the conventionally fixed samples and the freeze-substituted samples, including the lateral membrane system of the cochlear outer hair cells consisting of the lateral plasma membrane, pillars, cytoskeletal lattice and subsurface cysternae. However, some ultrastructural differences were found in the cells prepared by the freeze-substitution method. Electron-dense mosaic structures were found in the lumen of the tubules of the subsurface cysternae. Tangential sections of the tubules of the subsurface cysternae showed spirally wound parallel rows of electron-dense materials. In a rectangularly cut membrane with a trilaminar structure, the electron-dense materials appeared to be triangular protrusions from the outer leaflet of the unit membrane. These structures suggest that the subsurface cysternae may play an important role in the contraction of cochlear outer hair cells.

Animals↗
PubMed1994

F-actin, tubulin and spectrin in the organ of Corti: comparative distribution in different cell types and mammalian species.

Laser scanning confocal microscopy was used to determine the distribution of actin, spectrin and tubulin in whole mounts of the organ of Corti of guinea pig, monkey, rat and chinchilla. Actin, spectrin and tubulin were localized in all cell types in the auditory epithelium. No specialized cytoskeletal organization of tubulin was detected in the cytoplasmic domain of hair cells. The only specialized organization of actin and spectrin in the cytoplasmic domain was the infra-cuticular network, found exclusively in apical guinea pig outer hair cells. In contrast, the lateral wall of inner and outer hair cells contained a homogeneous distribution of label specific for actin and spectrin. The label intensity was similar in the base and the apex of the cochlea. These results indicate that the distribution of spectrin and actin in the auditory epithelium is similar to that in other epithelial cells, suggesting that actin and spectrin participate in the formation of cellular shape and possibly in docking molecules to the membrane.

Actins↗
PubMedDate not supplied

The role of thyroxine in the differentiation of the organ of Corti.

The developmental basis of the association of congenital deafness with hypothyroidism observed in several human syndromes was earlier investigated by experiments on mice. The offspring of females with chemically induced hypothyroidism were found to have malformations of the organ of Corti, showing that thyroxine played a role in the differentiation of this organ. The present study was undertaken to identify the site of action of the hormone in the developing organ. It appears to be the epithelium of the inner spiral sulcus.

Abnormalities, Drug-Induced↗
PubMed1989

[Ultrastructure of the human corpse Corti's organ].

Human cochlea locates deeply in the petrous part of the temporal bone, which makes the specimen preparation for electron microscopic study very difficult. The authors had collected two cochleas from human corpses died of brain injuries in order to know if the method of specimen preparation conventionally used was adequate for the preservation of ultrastructures and to study the ultrastructural characteristics of the human Corti's organ. The results showed that the specimen dissected 1 hour after death, stored at 4 degrees C and perfused with glutaraldehyde 4 hours after death was good enough in terms of preservation of fine structures. The authors had also compared their findings with those reported by others and those found in the guinea pig.

Animals↗
PubMedDate not supplied

Outer hair cells isolated from the organ of corti exposed to increased hydrostatic pressure.

A model using outer hair cells isolated from the guinea pig organ of Corti was used to study the effects of changes in hydrostatic pressure. Outer hair cells were placed in a closed chamber and the pressure was raised to levels corresponding to pressures measured inside the cochlea or higher. No changes in cell shape could be detected using either videomicroscopy or confocal microscopy. No clear changes were observed using a potentiometric vital dye.

Animals↗