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M Ulfendahl

Publications and source records attributed to M Ulfendahl.

At least 37 records · Page 2Linked to original sources
PubMed1997

["The cochlear amplifier". A crucial component of the hearing mechanism].

The function of the normal hearing organ; as reflected in electrophysiological recordings from the auditory nerve, is characterised by high sensitivity, fine frequency selectivity (tuning), and the presence of non-linearities. These characteristics are already manifest prior to the neural responses, however, and have now been observed in the mechanics of the cochlea in recordings from the organ itself. Cochlear mechanics are linked to the vulnerable 'cochlear amplifier' and the motile capacity of the sensory outer hair cells. Exposure to intense sound or ototoxic drugs may damage the outer hair cells, thus drastically changing both mechanical and electrophysiological responses of the inner ear. The active part played by the outer hair cells is strikingly exemplified by the so-called otoacoustic emissions, the sounds produced by the hearing organ itself even in the absence of external stimuli.

Cochlea↗
PubMed1997

Mechanical responses of the mammalian cochlea.

Recent findings in auditory research have significantly changed our views of the processes involved in hearing. Novel techniques and new approaches to investigate the mammalian cochlea have expanded our knowledge about the mechanical events occurring at physiologically relevant stimulus intensities. Experiments performed in the apical, low-frequency regions demonstrate that although there is a change in the mechanical responses along the cochlea, the fundamental characteristics are similar across the frequency range. The mechanical responses to sound stimulation exhibit tuning properties comparable to those measured intracellularly or from nerve fibres. Non-linearities in the mechanical responses have now clearly been observed at all cochlear locations. The mechanics of the cochlea are vulnerable, and dramatic changes are seen especially when the sensory hair cells are affected, for example, following acoustic overstimulation or exposure to ototoxic compounds such as furosemide. The results suggest that there is a sharply tuned and vulnerable response related to the hair cells, superimposed on a more robust, broadly tuned response. Studies of the micromechanical behaviour down to the cellular level have demonstrated significant differences radially across the hearing organ and have provided new information on the important mechanical interactions with the tectorial membrane. There is now ample evidence of reverse transduction in the auditory periphery, i.e. the cochlea does not only receive and detect mechanical stimuli but can itself produce mechanical motion. Hence, it has been shown that electrical stimulation elicits motion within the cochlea very similar to that evoked by sound. In addition, the presence of acoustically-evoked displacements of the hearing organ have now been demonstrated by several laboratories.

Acoustic Stimulation↗
PubMed1997

Pressure-induced basilar membrane position shifts and the stimulus-evoked potentials in the low-frequency region of the guinea pig cochlea.

We have used the guinea pig isolated temporal bone preparation to investigate changes in the non-linear properties of the tone-evoked cochlear potentials during reversible step displacements of the basilar membrane towards either the scala tympani or the scala vestibuli. The position shifts were produced by changing the hydrostatic pressure in the scala tympani. The pressures involved were calculated from measurements of the fluid flow through the system, and the cochlear DC impedance calculated (1.5 x 10(11) kg m-4 s-1, n = 10). Confocal microscopic visualization of the organ of Corti showed that pressure increases in the scala tympani caused alterations of the position of the reticular lamina and stereocilia bundles. For low pressures, there was a sigmoidal relation between the DC pressure applied to the scala tympani (and thus the position shift of the organ of Corti) and the amplitude of the summating potential. The cochlear microphonic potential also showed a pronounced dependence on the applied pressure: pressure changes altered the amplitude of the fundamental as well as its harmonics. In addition, the sound pressure level at which the responses began to saturate was increased, implying a transition towards a linear behaviour. An increase of the phase lag of the cochlear microphonic potential was seen when the basilar membrane was shifted towards the scala vestibuli. We have also measured the intracochlear DC pressure using piezoresistive pressure transducers. The results are discussed in terms of changes in the non-linear properties of cochlear transduction. In addition, the implications of these results for the pathophysiology and diagnosis of Meniérè's disease are discussed.

Acoustic Stimulation↗
PubMed1997

Relationship between stiffness, internal cell pressure and shape of outer hair cells isolated from the guinea-pig hearing organ.

The mechanical properties of outer hair cells are of importance for normal hearing, and it has been shown that damage of the cells can lead to a reduction in the hearing sensitivity. In this study, we measured the stiffness of isolated outer hair cells in hyper- and hypotonic conditions, and examined the change in stiffness in relation to the corresponding changes in internal cell pressure and cell shape. The results showed that the axial stiffness of isolated outer hair cells (30-90 microns in length, 8-12 microns in diameter), ranging from 0.13-5.39 mN m-1, was inversely related to cell length. Exposure to hyper- and hypotonic external media with a small percentage change in osmolality caused a similar magnitude of change in cell length and cell diameter, but an average 60% change in cell stiffness. Therefore, a moderate osmotic change in the external medium can lead to a significant alteration in cell stiffness. The findings thus indicate an important contribution of internal cell pressure to cell stiffness.

Animals↗
PubMed1996

The vibration pattern of the hearing organ in the waltzing guinea-pig measured using laser heterodyne interferometry.

The mechanical tuning characteristics of the hearing organ were measured in response to sound stimulation using laser heterodyne interferometry in in vitro preparations of temporal bones from waltzing guinea-pigs expressing different degrees of hearing organ and sensory cell degeneration. Measurements were made at various stages of structural changes allowing us to correlate structure and mechanical function. It was found that the characteristic frequency of the response at a given location in the cochlea occurred at lower frequencies than what is normally seen and that the sharpness of the mechanical tuning was considerably reduced when sensory hair cells were absent and the hearing organ structurally altered. However, even when extensive hair cell degeneration was evident a residual mechanical tuning was present. These results further support the concept that the sensory hair cells plays a key role in determining normal auditory tuning characteristics. It is suggested that the basilar membrane mechanics gives rise to a broadly tuned mechanical response on which a sharper tuning mechanism, originating from the hair cells, is superimposed.

Acoustic Stimulation↗
PubMed1996

The cellular localization of the neuropeptides substance P, neurokinin A, calcitonin gene-related peptide and neuropeptide Y in guinea-pig vestibular sensory organs: a high-resolution confocal microscopy study.

Four neuropeptides, substance P, neurokinin A, calcitonin gene-related peptide and neuropeptide Y, were detected by radioimmunoassay in guinea-pig vestibular end-organs. High-resolution confocal microscopy visualization of immunofluorescence staining was used to determine the cellular localization of these peptides. Substance P- and neurokinin A-like immunoreactivities were found to co-exist in afferent fibers innervating the peripheral regions of both the utricular and ampullar sensory organs. The immunoreactivity was more concentrated in the distal ends of the calyceal-shaped nerve endings that innervate type I sensory cells. While in the guinea-pig, nerve calyces and type I cells are distributed in both the central and peripheral regions of the sensory epithelia, immunoreactive calyces were found only in the peripheral regions. Calcitonin gene-related peptide-like immunoreactivity was localized in small bouton endings situated at the level of the base of the hair cells. These boutons were in a position to make axosomatic contacts with type II sensory cells and axodendritic contacts with afferent nerve endings. Calcitonin gene-related peptide immunoreactivity co-existed with choline acetyltransferase immunoreactivity. The localization and shape of these boutons identified them as the axonal endings of efferent vestibular fibers. Neuropeptide Y-like immunoreactivity was not observed in the actual sensory epithelium but in the underlying connective tissue, where it was located in varicose fibers along blood vessels. The synaptic position of the tachykinins is clearly distinct from that of calcitonin gene-related peptide. This segregation distinguishes the vestibular end-organs from most peripheral tissues where these peptides are co-localized. The tachykinin-immunoreactive afferent fibers are postsynaptic to the hair cells. If, as in somatic sensory endings, these fibers can be triggered to release the neuropeptides by an axon reflex type of activation, then the tachykinins could interfere directly with the function of type I and type II vestibular hair cells. Calcitonin gene-related peptide co-exists with acetylcholine in the efferent axonal endings that are presynaptic to type II hair cells and to afferent fibers. Calcitonin gene-related peptide can thus interfere by direct synaptic action with type II hair cells only. It may also regulate the activity of the tachykinin-containing afferents.

Animals↗
PubMed1996

Acoustically induced vibrations of the Reissner's membrane in the guinea-pig inner ear.

In the inner ear, the Reissner's membrane separates the scala vestibuli from the scala media and is thus of importance for maintaining a positive endocochlear potential. The motion of the membrane is thought to be driven by the vibrations of the underlying hearing organ caused by a hydromechanical coupling between the structures. Since the Reissner's membrane is relatively easily accessible in the cochlea its vibratory response has been used as a measure of the micromechanical behaviour of the hearing organ. To determine whether this indirect measure revealed the true characteristics of the hearing organ, experiments were performed using laser heterodyne interferometry in an in vitro preparation of the guinea-pig temporal bone. Interferometric measurements at the Reissner's membrane and at the surface of the hearing organ directly beneath made it possible to compare the mechanical tuning characteristics of both structures. It was found that the mechanical response characteristics of the Reissner's membrane differed considerably from the hearing organ. The tuning frequency was different and only minor changes in the maximal vibration amplitude were seen when measuring at different radial locations. However, the shape of the response curve changes with location. The Reissner's membrane response appeared to be affected by the mechanical vibrations originating both at the middle ear ossicles and at the hearing organ. It is concluded that the Reissner's membrane response is a poor indicator of cochlear mechanics and that investigations of cochlear micromechanics should be performed directly at the level of the hearing organ.

Acoustic Stimulation↗
PubMed1996

Mechanical response characteristics of the hearing organ in the low-frequency regions of the cochlea.

1. With the use of an in vitro preparation of the guinea pig temporal bone, in which the apical turns of the cochlea are exposed, the mechanical and electrical responses of the cochlea in the low-frequency regions were studied during sound stimulation. 2. The mechanical characteristics were investigated in the fourth and third turns of the cochlea with the use of laser heterodyne interferometry, which allows the vibratory responses of both sensory and supporting cells to be recorded. The electrical responses, which can be maintained for several hours, were recorded only in the most apical turn. 3. In the most apical turn, the frequency locations and shapes of the mechanical and electrical responses were very similar. 4. The shapes of the tuning curves and the spatial locations of the frequency maxima in the temporal bone preparation compared very favorably with published results from in vivo recordings of hair cell receptor potentials and sound-induced vibrations of the Reissner's membrane. 5. Compressive nonlinearities were present in both the mechanical and the electrical responses at moderate sound pressure levels. 6. The mechanical tuning changed along the length of the cochlea, the center frequencies in the fourth and third turns being approximately 280 and 570 Hz, respectively. 7. The mechanical responses of sensory and supporting cells were almost identical in shape but differed significantly in amplitude radially across the reticular lamina.

Acoustic Stimulation↗
PubMed1996

Acute mechanical overstimulation of isolated outer hair cells causes changes in intracellular calcium levels without shape changes.

Impaired auditory function following acoustic overstimulation, or noise, is mainly reported to be accompanied by cellular changes such as damage to the sensory hair bundles, but changes in the cell bodies of the outer hair cells have also been described. To investigate more closely the immediate cellular responses to overstimulation, isolated guinea pig outer hair cells were subjected to a 200 Hz oscillating water jet producing intense mechanical stimulation. The water jet was aimed at the cell body of the isolated outer hair cell. Cell shape changes were studied using video microscopy, and intracellular calcium concentration changes were monitored by means of the fluorescent calcium indicator Fluo-3. Cells exposed to a high-intensity stimulus showed surprisingly small light-microscopical alterations. The cytoplasmic calcium concentration increased in most cells, although some cells appeared very resistant to the mechanical stress. No correlation could be found be tween the calcium concentration changes and the cell length. The changes in calcium concentration reported here are suggested to be involved in the long-term pathogenesis of noise-induced hair cell damage.

Acoustic Stimulation↗
PubMed1995

Shearing motion in the hearing organ measured by confocal laser heterodyne interferometry.

To investigate the presence of the postulated shearing motion in the micromechanics of the inner ear during sound stimulations we measured the vibratory response of the tectorial membrane and the reticular lamina in the third cochlear turn in an isolated temporal bone preparation using confocal laser heterodyne interferometry. The mechanical response of the tectorial membrane had the same frequency of maxima as the underlying reticular lamina, but was not as sharply tuned. When the two-dimensional motion was calculated from measurements made from several viewing angles it was found that the vibration of the reticular lamina had significant components both normal and tangential to its surface. The tectorial membrane motion, however, was primarily in a direction approximately perpendicular to the surface of the reticular lamina. The results indicate that shearing motion is produced predominantly by the radial motion of the reticular lamina.

Acoustic Stimulation↗
PubMed1993

Changes in the mechanical tuning characteristics of the hearing organ following acoustic overstimulation.

An in vitro preparation of the guinea-pig temporal bone was used to study the effects of acoustic overstimulation on the mechanical tuning characteristics of the inner ear. Using laser heterodyne interferometry, the vibratory responses of selected sensory and supporting cells within the hearing organ were measured in response to acoustic signals applied to the ear to obtain mechanical tuning curves before and after applying acoustic overstimulation. Following overstimulation the frequency at which the maximal vibration response occurred moved towards lower frequencies, the vibration amplitude generally increased and the shape of the mechanical tuning curves became considerably flatter. These effects were seen within minutes of overstimulation. The micromechanical changes were accompanied by distinct morphological changes mainly affecting the first row of outer hair cells, which were swollen and shortened. Hensen bodies and swelling of the subsurface cisternae were observed in the affected cells. Apart from this, most of the shortened cells looked structurally intact, had undamaged sensory hair bundles and made synaptic contacts to both afferent and efferent nerve fibres. The results demonstrate that the outer hair cells play a key role in determining the tuning of the hearing organ.

Acoustic Stimulation↗
PubMed1993

Mechanical tuning characteristics of the hearing organ measured at the sensory cells in the gerbil temporal bone preparation.

The micromechanical behaviour of the inner ear in response to sound stimulation was investigated in an in vitro preparation of the gerbil temporal bone. Using laser heterodyne interferometry it was possible to measure the vibration responses directly at the level of the sensory and supporting cells within the hearing organ rather than from the underlying basilar membrane as has been done in previous studies. There was a tuned mechanical response of the cellular structures within the hearing organ. The resonance frequency measured at cells in the apical (third) turn was around 200Hz. The frequency of the mechanical tuning varied along the length of the cochlea. In the second turn the resonance frequency was around 500-700Hz. The cellular response in the second turn was more sharply tuned as compared to the response in the apical turn. In both cochlear turns the amplitude of the vibratory response changed with the cellular location radially across the hearing organ.

Acoustic Stimulation↗
PubMed1993

Evidence for calcium-binding proteins and calcium-dependent regulatory proteins in sensory cells of the organ of Corti.

Calcium is thought to play a major signaling role in outer hair cells to control metabolism, cytoskeletal integrity, cell shape and cell excitability. For this to happen, in resting cells the concentration of free calcium ions must be maintained at low levels so that focal increases can trigger specific events. In this paper, the localization of calcium, calcium-binding and calcium-dependent regulatory proteins in sensory cells from the guinea pig inner ear was demonstrated using immunocytochemical and histochemical techniques. We found the calcium buffer and/or calcium sensor proteins calmodulin, calbindin and calsequestrin predominantly in sensory cells and that when present, these proteins can be enriched in the outer hair cells. Calmodulin is found in the stereocilia, in the cuticular plate and in the cytoplasm and calbindin is found only in the cuticular plate and cytoplasm of both the inner and outer hair cells. The staining for these proteins in the outer hair cells is homogeneous, with no apparent compartmentalization along the lateral wall. Calsequestrin, thought to store and release calcium from membrane bound intracellular storage sites is found only in the cytoplasm of outer hair cells. There, it has a more punctuate staining pattern than does calmodulin or calbindin suggesting that it may be present in calciosomes rather than soluble in the cytoplasm. We did not detect caldesmon and S-100. Using the potassium pyroantimonate technique, we found precipitates containing calcium ions distributed throughout the cytoplasm of outer hair cells, with no evidence that the subsurface cisterns along the lateral wall act as calcium storage sites. Thus, calcium in resting cells is found in the cytoplasm along with calbindin and calmodulin and appears to have a punctate distribution consistent with a co-localization with calsequestrin. The implications of this distribution with respect to the slow shortening and elongation seen in outer hair cells are discussed.

Animals↗
PubMed1993

Spontaneous cellular vibrations in the guinea-pig cochlea.

Mechanical vibrations of Hensen cells were measured with a laser-heterodyne interferometer in the third turn of the guinea-pig temporal-bone preparation without the application of an external stimulus. Smoothed periodograms (spectral-density estimates vs frequency) were constructed from the velocity vs time waveforms recorded from individual cells. For some cells, several peaks appear in the periodograms at levels as high as 10 dB above the noise floor, indicating the presence of spontaneous vibrations. The frequencies at which the peaks are located differ in different preparations, indicating that the observed peaks are not caused by the presence of ambient noise or ambient vibrations. It is demonstrated that smoothed-periodogram analysis is superior to fast-Fourier-transform analysis for discerning these spontaneous spectral components. The frequency tuning curves of cells from which spontaneous vibrations were measured (determined by applying an external stimulus to the ear) have single principal peaks. When the spontaneous spectral features are present, their frequencies lie, for the most part, within the principal-peak region of the tuning curve. We propose that these spontaneous vibrations originate at the outer hair cells and are the source of spontaneous otoacoustic emissions in the ear.

Animals↗
PubMed1993

Spontaneous cellular vibrations in the guinea-pig temporal-bone preparation.

Mechanical vibrations of Hensen cells were measured with a laser-heterodyne interferometer in the guinea-pig temporal-bone preparation without the application of an external acoustic stimulus. Smoothed periodograms (spectral-density estimates v. frequency) were constructed from the velocity v. time waveforms recorded from individual cells. Several peaks were seen in the periodograms at levels as high as 10 dB above the noise floor, indicating the presence of spontaneous vibrations. The frequencies at which the peaks were located differed in different preparations, indicating that the observed peaks were not caused by the presence of ambient noise or ambient vibrations. Furthermore, vibrations were seen only in fresh preparations. The tuning curves of cells from which spontaneous vibrations were measured (determined by applying an external stimulus to the ear) had single principal peaks. Several peaks in the periodogram were found to be located within the principal-peak region of the tuning curve. The spontaneous response does not arise from noise filtered through the tuning curve which would have a single peak. We propose that these spontaneous vibrations originate at the outer hair cells and are the source of spontaneous otoacoustic emissions in the ear.

Animals↗
PubMed1992

The tuned displacement response of the hearing organ is generated by the outer hair cells.

The motile responses of the guinea-pig hearing organ in response to a tone applied to the ear were measured by laser interferometry. Two types of responses can be recorded: (i) a vibration at the frequency of the applied tone; and (ii) a displacement response consisting of a shift in the position of the organ surface. The purpose of this study is to characterize the displacement response. The results are as follows. There is a relationship between the frequency of highest sensitivity (best-frequency) of the displacement response and the site from which it is recorded. High best-frequencies are noticed at more basal locations, low best-frequencies towards the apex. The displacement response is more frequency-selective than the vibration response. The displacement response is observed within physiological sound pressure levels. Its sharpness is dependent on the stimulus intensity, it shows biological variability and can be manipulated by drugs that are known to modify the receptor potential of the sensory cells, or to interfere with outer hair cell motility. These results suggest that the displacement response is an important step in the transduction process in the mammalian hearing organ and that it is generated by the motile action of the outer hair cells.

Acoustic Stimulation↗
PubMed1992

Actin-binding and microtubule-associated proteins in the organ of Corti.

Actin-binding and microtubule-associated proteins regulate microfilament and microtubule number, length, organization and location in cells. In freeze-dried preparations of the guinea pig cochlea, both actin and tubulin are found in the sensory and supporting cells of the organ of Corti. Fodrin (brain spectrin) co-localized with actin in the cuticular plates of both inner and outer hair cells and along the lateral wall of the outer hair cells. Alpha-actinin co-localized with actin in the cuticular plates of the hair cells and in the head and foot plates of the supporting cells. It was also found in the junctional regions between hair cells and supporting cells. Profilin co-localized with actin in the cuticular plates of the sensory hair cells. Myosin was detected only in the cuticular plates of the outer hair cells and in the supporting cells in the region facing endolymph. Gelsolin was found in the region of the nerve fibers. Tubulin is found in microtubules in all cells of the organ of Corti. In supporting cells, microtubules are bundled together with actin microfilaments and tropomyosin, as well as being present as individual microtubules arranged in networks. An intensely stained network of microtubules is found in both outer and inner sensory hair cells. The microtubules in the outer hair cells appear to course throughout the entire length of the cells, and based on their staining with antibodies to the tyrosinated form of tubulin they appear to be more dynamic structures than the microtubules in the supporting cells. The microtubule-associated protein MAP-2 is present only in outer hair cells within the organ of Corti and co-localizes with tubulin in these cells. No other MAPs (1,3,4,5) are present. Tau is found in the nerve fibers below both inner and outer hair cells and in the osseous spiral lamina. It is clear that the actin-binding and microtubule-associated proteins present in the cochlea co-localize with actin and tubulin and that they modulate microfilament and microtubule structure and function in a manner similar to that seen in other cell types. The location of some of these proteins in outer hair cells suggests a role for microfilaments and microtubules in outer hair cell motility.

Actinin↗