Search PubMed⌕ Search

Biomedical subjects

P Dallos

Publications and source records attributed to P Dallos.

At least 37 records · Page 2Linked to original sources
PubMed1999

Response phase: a view from the inner hair cell.

Inner hair cell (IHC) responses are recorded from the apical three turns of the guinea pig cochlea in order to define the relationship between hair cell depolarization and position of the basilar membrane. At low frequencies, inner hair cell depolarization is generally observed near basilar membrane velocity to scala vestibuli, reflecting the putative freestanding nature of the IHC's stereocilia. While this is consistent with previous IHC results, independent of location, and with neural responses for fibers with low best frequencies, it is inconsistent with single-unit results from the base of the cochlea, where response phase is associated with basilar membrane velocity to scala tympani. Results suggest that the temporal disparity between IHC and neural data from the base of the cochlea may relate to several factors that influence transmembrane voltage in IHCs. First, extracellular voltages (Ingvarsson, 1981; Sellick et al., 1982; Russell and Sellick, 1983) can potentially affect low- and high-frequency regions differently because electrical interactions are more likely in the base of the cochlea than in the apex (Dallos, 1983, 1985). Second, waveform distortion and kinetic properties associated with voltage-dependent ion channels in the IHC's basolateral membrane can both influence response phase by adding harmonic components and lagging the receptor potential by as much as 90 deg. Third, the velocity dependence of IHCs in the apex appears to extend to higher frequencies than the velocity dependence demonstrated for IHCs in the base of the cochlea. These features, which influence the timing of discharges in the auditory nerve, are compared and evaluated.

Animals↗
PubMed1999

Development of acetylcholine-induced responses in neonatal gerbil outer hair cells.

Cochlear outer hair cells (OHCs) are dominantly innervated by efferents, with acetylcholine (ACh) being their principal neurotransmitter. ACh activation of the cholinergic receptors on isolated OHCs induces calcium influx through the ionotropic receptors, followed by a large outward K+ current through nearby Ca2+-activated K+ channels. The outward K+ current hyperpolarizes the cell, resulting in the fast inhibitory effects of efferent action. Although the ACh receptors (AChRs) in adult OHCs have been identified and the ACh-induced current responses have been characterized, it is unclear when the ACh-induced current responses occur during development. In this study we attempt to address this question by determining the time of onset of the ACh-induced currents in neonatal gerbil OHCs, using whole cell patch-clamp techniques. Developing gerbils ranging in age from 4 to 12 days were used in these experiments, because efferent synaptogenesis and functional maturation of OHCs occur after birth. Results show that the first detectable ACh-induced current occurred at 6 days after birth (DAB) in 12% of the basal turn cells with a small outward current. The fraction of responsive cells and the size of outward currents increased as development progressed. By 11 DAB, the fraction of responsive cells and the current size were comparable with those of adult OHCs. The results indicate that the maturation of the ACh-induced response begins around 6 DAB. It appears that the development of ACh-induced responses occur during the same time period when OHCs develop motility but before the onset of auditory function, which is around 12 DAB when cochlear microphonic potentials can first be evoked with acoustic stimulation in gerbils.

Acetylcholine↗
PubMed1999

Direct visualization of organ of corti kinematics in a hemicochlea.

The basilar membrane in the mammalian cochlea vibrates when the cochlea receives a sound stimulus. This mechanical vibration is transduced into hair cell receptor potentials and thereafter encoded by action potentials in the auditory nerve. Knowledge of the mechanical transformation that converts basilar membrane vibration into hair cell stimulation has been limited, until recently, to hypothetical geometric models. Experimental observations are largely lacking to prove or disprove the validity of these models. We have developed a hemicochlea preparation to visualize the kinematics of the cochlear micromechanism. Direct mechanical drive of 1-2 Hz sinusoidal command was applied to the basilar membrane. Vibration patterns of the basilar membrane, inner and outer hair cells, supporting cells, and tectorial membrane have been recorded concurrently by means of a video optical flow technique. Basilar membrane vibration was driven in a direction transversal to its plane. However, the direction of the resulting vibration was found to be essentially radial at the level of the reticular lamina and cuticular plates of inner and outer hair cells. The tectorial membrane vibration was mainly transversal. The transmission ratio between cilia displacement of inner and outer hair cells and basilar membrane vibration is in the range of 0.7-1.1. These observations support, in part, the classical geometric models at low frequencies. However, there appears to be less tectorial membrane motion than predicted, and it is largely in the transversal direction.

Animals↗
PubMed1998

Morphology of the unfixed cochlea.

Our knowledge of cochlear geometry is based largely upon anatomical observations derived from fixed, dehydrated, embedded and/or sputter-coated material. We have now developed a novel preparation, the hemicochlea, where for the first time living cochlear structures can be observed in situ and from a radial perspective. The experiments were performed on the Mongolian gerbil. Ion substitution experiments suggest that no significant swelling or shrinkage occurs when the preparation is bathed in normal culture medium, so long as calcium concentration is kept at endolymph-like (20 microM) levels. The tectorial membrane-reticular lamina relationship appears to remain well preserved. Hensen's stripe maintains a close relationship with the inner hair cell stereociliary bundle, unless the mechanical coupling becomes disturbed. In addition, standard fixation and/or dehydration procedures are used to quantify changes due to shrinkage artifacts. Various morphometric gradients are examined in unfixed specimens from apical, middle, and basal turns.

Animals↗
PubMed1998

The level dependence of response phase: observations from cochlear hair cells.

Hair cell responses are recorded from third turn of the guinea pig cochlea in order to define the relationship between hair cell depolarization and position of the basilar membrane. Because the latter is determined locally, using the cochlear microphonic recorded in the organ of Corti (OC) fluid space, no corrections are required to compensate traveling wave and/or synaptic delays. At low levels, inner hair cells (IHC) depolarize near basilar membrane velocity to scala vestibuli reflecting the free standing nature of their stereocilia. At high levels, the time of depolarization changes rapidly from velocity to scala vestibuli to the scala tympani phase of the basilar membrane response. This change in response phase, recorded in the fundamental component of the IHC response, is associated with a decrease in response magnitude. The absence of this behavior in OC and outer hair cell responses implies that basilar membrane mechanics may not be responsible for these response patterns. Because these features are reminiscent of the magnitude notches and the large phase shifts observed in single unit responses at high stimulus levels, they provide the IHC correlates of these phenomena.

Acoustic Stimulation↗
PubMed1998

Basilar membrane vibration in the gerbil hemicochlea.

Excised gerbil cochleae were cut along the mid-modiolar plane (hemicochlea). Along one-half turn of this preparation, fluorescent microbeads were placed on the basilar membrane (BM). The BM was vibrated with click stimuli (50 micros) produced mechanically by a piezo pusher. The stimulus delivery probe could be positioned either more apical or more basal from the beads. Vibration patterns were measured with a wide bandwidth photomultiplier from the movements of the beads. When the probe was positioned more basal, the responses to click stimuli were brief, damped sinusoids. According to the fast Fourier transforms (FFTs) of the averaged time wave forms, the best frequency between successive beads decreased toward the apex (0.8 octave/mm). Sharpness of tuning of the normalized FFT spectra (NQ10dB) on average was 1.5. Response amplitude at a fixed input level, measured at different beads away from the stimulation site, dropped exponentially (58 dB/mm). In addition, for each individual bead, amplitude dropped linearly with decreasing stimulus intensity. In experiments where the stimulating probe was placed more apical, two major properties were observed: first, beads revealed only the spectral components present in the motion of the probe. Second, magnitude reduction of the displacement of the cochlear partition was greater, on average 155 dB/mm, indicating a lack of significant propagation in the reverse direction.

Acoustic Stimulation↗
PubMed1997

Expression of potassium channels in gerbil outer hair cells during development does not require neural induction.

Mammalian outer hair cells (OHCs) contain Ca and K channels in their synaptic pole. We questioned if the ontogeny of potassium currents of OHCs depends on the neural induction of early afferent contact. By recording whole-cell currents of OHCs grown in organotypic cultures deprived of afferent innervation, we show that a Ca-activated K channel is expressed in these cells, suggesting that the ontogeny of the K channel is an intrinsic process.

Animals↗
PubMed1997

Acetylcholine, outer hair cell electromotility, and the cochlear amplifier.

The dominant efferent innervation of the cochlea terminates on outer hair cells (OHCs), with acetylcholine (ACh) being its principal neurotransmitter. OHCs respond with a somatic shape change to alterations in their membrane potential, and this electromotile response is believed to provide mechanical feedback to the basilar membrane. We examine the effects of ACh on electromotile responses in isolated OHCs and attempt to deduce the mechanism of ACh action. Axial electromotile amplitude and cell compliance increase in the presence of the ligand. This response occurs with a significantly greater latency than membrane current and potential changes attributable to ACh and is contemporaneous with Ca2+ release from intracellular stores. It is likely that increased axial compliance largely accounts for the increase in motility. The mechanical responses are probably related to a recently demonstrated slow efferent effect. The implications of the present findings related to commonly assumed efferent behavior in vivo are considered.

Acetylcholine↗
PubMed1997

Low-frequency modulation of inner hair cell and organ of Corti responses in the guinea pig cochlea.

Low-frequency tones are used to study changes in responsiveness as a function of phase in inner hair cell (IHC) and organ of Corti (OC) responses recorded from second turn of the guinea pig cochlea. In these experiments a 40 Hz stimulus is combined with a variable frequency probe to determine the degree to which tones at and below best frequency (BF) are modulated. Changes in responsiveness produced by the low-frequency input are quantified and related to position of the basilar membrane which is estimated using the phase of the cochlear microphonic measured in the OC fluid space. Results obtained when 40 Hz is presented at its lowest effective level demonstrate that ac responses to low-level BF probes are reduced for basilar membrane displacements to scala tympani while probe tones well below BF are modulated in the opposite direction. The transition between these two response patterns occurs when the overall DC produced in the OC by the two-tone input changes from positive to negative. Because of this association, the frequency dependence exhibited in the bias results may be linked to mechanisms responsible for generating the two polarities of the summating potential and the DC receptor potentials that it reflects. An attempt is also made to relate bias-induced changes in hair cell receptor potentials to modulations in single-unit rate responses. In other words, to address variations in the temporal relationships between excitation and suppression measured in the auditory nerve.

Acoustic Stimulation↗
PubMed1997

Intermodulation components in inner hair cell and organ of Corti responses.

Two-tone responses are recorded from inner hair cells and from the organ of Corti fluid space in second and third turns of the guinea pig cochlea where best frequencies (BF) are approximately 4000 and 1000 Hz, respectively. This allows both ac and dc response components to be obtained and facilitates comparisons with psychophysical investigations that have traditionally been conducted at low and moderate frequencies. The measurements of ac responses in the organ of Corti fluid space also allow comparisons with mechanical results because the cochlear microphonic is proportional to basilar membrane displacement. By using a constant frequency ratio (f2/f1) of 1.4, local distortion products generated at the recording location are prominent when the two primaries are near the BF of the cell. However, when the primary pairs increase above BF, quadratic and cubic difference tones are recorded even when responses to the primaries are not measurable. The presence of these traveling distortion products is consistent with the idea that both f2-f1 and 2f1-f2 have their own traveling waves. Notches in the existence regions of quadratic and cubic difference tones were also observed and found to be influenced by mutual suppression between the two inputs.

Acoustic Stimulation↗
PubMed1997

Hyposmotic swelling induces magnitude and gain change in the electromotile performance of isolated outer hair cells.

OHCs were inserted into a partitioning microchamber. Reversible swelling was induced by hyposmotic incubation medium (270 mos.kg H2O-1). The transfer curve of electromotility was measured by stimulating the OHCs with a series of brief (2.5 ms) square-pulses with both polarities and graded magnitudes. Response magnitude and gain of electromotility were increased in swollen OHCs. On the basis of their electromotile performance-characteristics, swelling appeared to depolarize the OHCs. Transition from contraction dominated asymmetry of motility was observed towards a symmetric response. Depolarization, by itself, cannot explain the gain and magnitude increase. Acetylcholine (ACh) responsiveness of swollen OHCs preserves the pre-challenged pattern: ACh further increases gain and magnitude.

Acetylcholine↗
PubMed1997

Outer hair cells: the inside story.

The neurobiology of hair cells is reviewed, including their transduction apparatus, the production and nature of receptor potentials, and the similarities and differences between inner hair cells and outer cells (OHCs). Intracellular recordings from hair cells in vivo are discussed. This is followed by a consideration of effects of OHC lesions and consequent notions about OHC functions. Feedback in the cochlea is then considered, and the role of OHCs as the feedback element is examined, along with putative means of producing the feedback.

Animals↗
PubMed1996

Effect of acetylcholine and GABA on the transfer function of electromotility in isolated outer hair cells.

Outer hair cells (OHC) from high- and low-frequency regions were separately isolated from guinea pig cochleas. The cells were inserted with their ciliary pole first into a partitioning microchamber so that only 20-50% of the cell length was excluded. Somatic length changes due to transcellular electrical stimulation were measured at the cuticular plate in the inserted portion of the cells. Transfer curves of electromotility of the OHCs were obtained by both a series of brief (2.5 ms) and longer (30 ms) square pulses with opposite polarity and linearly increasing size from 40 to 280 mV in both negative and positive directions. Alterations in the transient and steady-state electromotility transfer curves were examined by application of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) to the synaptic pole. ACh, in the concentration range of 10-30 microM, evoked a significant magnitude and gain increase of electromotility in both transient and steady-state responses without a measurable shift in the operating point of the displacement-voltage transfer curve. A tonotopic response magnitude difference is found for ACh challenge. Basal turn OHCs responded with greater magnitude increase (+90% increase from control) than apical turn OHCs (+40%). GABA exerted an opposite effect, again in a location-dependent manner. Magnitude response decreased about 30% for long cells and 14% for short ones. Atropin, a muscarinic receptor antagonist, completely blocked the increase in electromotility response due to ACh. However, D-tubocurarine, a nicorinic receptor antagonist, while not blocking the ACh effect, altered the cell's apparent operating point. Bicuculline methiodide, a GABAA-receptor antagonist, completely arrested GABA influences on the electromotility response. These results suggest that both ACh and GABA can change the electromotile activity of OHCs, in a tonotopically biased manner. ACh challenge evokes greater magnitude responses in basal turn OHCs, whereas GABA induces greater motility response decrease in apical turn OHCs. The control of the gain and magnitude of electromotility by the transmitter substances appear to involve at least two mechanisms. One is probably related to conformational changes of the voltage-to-movement converter molecules and a change in their number in an effective operational pool, the other operates via changing the electrical resistance of the basolateral cell membrane.

Acetylcholine↗
PubMed1995

High-frequency motility of outer hair cells and the cochlear amplifier.

Outer hair cells undergo somatic elongation-contraction cycles in vitro when electrically stimulated. This "electromotile" response is assumed to underlie the high sensitivity and frequency selectivity of amplification in the mammalian cochlea. This process, presumably operating on a cycle-by-cycle basis at the frequency of the stimulus, is believed to provide mechanical feedback in vivo. However, if driven by the receptor potential of the cell, the mechanical feedback is expected to be severely attenuated at high frequencies because of electrical low-pass filtering by the outer hair cell basolateral membrane. It is proposed that electromotility at high frequencies is driven instead by extracellular potential gradients across the hair cell, and it is shown that this driving voltage is not subject to low-pass filtering and is sufficiently large. It is further shown that if the filtering properties of the cell membrane are canceled, taking advantage of the electrical characteristics of isolated outer hair cells in a partitioning glass microchamber, then the lower bound of the motor's bandwidth is approximately 22 kilohertz, a number determined only by the limitations of our instrumentation.

Acoustic Stimulation↗
PubMed1994

First appearance and development of electromotility in neonatal gerbil outer hair cells.

With the purpose of pinpointing the time of onset of electromotility, outer hair cells (OHCs) from apical and basal turns of the cochleae of postnatal gerbils, ranging in age from 6 to 19 days, were isolated and drawn into a glass microchamber. Length changes evoked by transcellular electrical stimulation were detected and measured with a photodiode detector. Motile responses first appeared in 3 out of 14 basal turn OHCs at 7 days after birth (DAB). At 8 DAB, 3 out of 13 apical turn cells also responded to the electrical stimulation. By 12 DAB, all the OHCs from both turns showed motile responses. Input-output functions relating applied stimulus and change in cell length revealed that the motile response threshold improved from 7 DAB to 12 DAB and the response amplitude kept increasing from 7 DAB until 13-14 DAB, when mature amplitudes were reached. Measurements of OHC length revealed only minor changes in basal turn hair cell length while apical hair cells continued to elongate until approximately 16 DAB. Since the onset of auditory function in gerbils occurs around 12 DAB and fine tuning develops between 14 and 17 DAB, our results suggest that the onset of OHC motility occurs earlier than that of auditory function and the maturation of the motility amplitude occurred earlier than the development of fine tuning. The maturation of OHC motility and the development of otoacoustic emissions are also compared and discussed.

Acoustic Stimulation↗
PubMed1994

Stimulus biasing: a comparison between cochlear hair cell and organ of Corti response patterns.

Responses from the organ of Corti (OC) fluid space and from individual hair cells are collected for short duration tone pips measured alone and in the presence of a 20 Hz bias tone. Because of the relatively long period of the acoustic bias signal, a probe can be selectively placed at precise locations within a single response period. Since bias effects produced during maximum basilar membrane velocity are negligible, this report documents changes associated with basilar membrane displacements to scala vestibuli and scala tympani. Hair cell response patterns are compared with those measured nearby in the OC to determine the degree to which inner (IHC) and outer hair cells (OHC) contribute to the gross cochlear potentials. It is shown that intracellular OHC and OC dc responses are strongly influenced by the bias while intracellular IHC dc responses are minimally affected. Although an association has been established between the cochlear microphonic and outer hair cell ac receptor potentials, the well correlated changes in the outer hair cell dc receptor potential and the organ of Corti summating potential suggest that gross cochlear potentials reflect dc as well as ac contributions from nearby OHCs. Since IHC responses are not influenced by the bias, they appear to contribute less than OHCs to extracellular potentials. These conclusions, however, are restricted to the moderately high input levels required to produce these effects (Durrant and Dallos, 1974) and to the central region of the cochlea where the recordings are made. Finally, the degree to which bias effects are contaminated by two-tone suppression is discussed.

Acoustic Stimulation↗
PubMed1993

Stereocilia displacement induced somatic motility of cochlear outer hair cells.

Outer hair cells, isolated from mammalian cochleas, are known to respond to electrical stimulation with elongation or contraction of the cell's cylindrical soma. It is assumed that such shape changes, when driven by the cell's receptor potential in vivo, are a part of the feedback process that underlies cochlear amplification. To date it has not been possible to demonstrate somatic shape changes upon normal mechanical stimulation of the cell--i.e., the deflection of its hair bundle. We show here that mechanically induced hair-bundle deflection produces somatic motility of the cell. Such motility is dependent upon a functioning forward transducer process and disappears upon interference with transduction. The motile response also reflects the hair bundle's known directional sensitivity. This demonstration of mechanically driven motility indicates that the cell may possess capabilities to affect its mechanical environment under control of its own receptor potential and, thereby, participate in a local cochlear feedback process.

Animals↗