Biomedical subjects

Andrei N Lukashkin

Publications and source records attributed to Andrei N Lukashkin.

8 recordsLinked to original sources

PubMed2007

Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane.

Frequency tuning in the cochlea is determined by the passive mechanical properties of the basilar membrane and active feedback from the outer hair cells, sensory-effector cells that detect and amplify sound-induced basilar membrane motions. The sensory hair bundles of the outer hair cells are imbedded in the tectorial membrane, a sheet of extracellular matrix that overlies the cochlea's sensory epithelium. The tectorial membrane contains radially organized collagen fibrils that are imbedded in an unusual striated-sheet matrix formed by two glycoproteins, alpha-tectorin (Tecta) and beta-tectorin (Tectb). In Tectb(-/-) mice the structure of the striated-sheet matrix is disrupted. Although these mice have a low-frequency hearing loss, basilar-membrane and neural tuning are both significantly enhanced in the high-frequency regions of the cochlea, with little loss in sensitivity. These findings can be attributed to a reduction in the acting mass of the tectorial membrane and reveal a new function for this structure in controlling interactions along the cochlea.

Animals↗

PubMed2005

A deafness mutation isolates a second role for the tectorial membrane in hearing.

Alpha-tectorin (encoded by Tecta) is a component of the tectorial membrane, an extracellular matrix of the cochlea. In humans, the Y1870C missense mutation in TECTA causes a 50- to 80-dB hearing loss. In transgenic mice with the Y1870C mutation in Tecta, the tectorial membrane's matrix structure is disrupted, and its adhesion zone is reduced in thickness. These abnormalities do not seriously influence the tectorial membrane's known role in ensuring that cochlear feedback is optimal, because the sensitivity and frequency tuning of the mechanical responses of the cochlea are little changed. However, neural thresholds are elevated, neural tuning is broadened, and a sharp decrease in sensitivity is seen at the tip of the neural tuning curve. Thus, using Tecta(Y1870C/+) mice, we have genetically isolated a second major role for the tectorial membrane in hearing: it enables the motion of the basilar membrane to optimally drive the inner hair cells at their best frequency.

Acoustic Stimulation↗

PubMed2005

A self-mixing laser-diode interferometer for measuring basilar membrane vibrations without opening the cochlea.

A laser-diode forms the basis of a displacement sensitive homodyne interferometer suitable for measurements from poorly reflective surfaces. The compact and cost-effective interferometer utilizes the self-mixing effect when laser light reflected from a moving target re-enters the laser cavity and causes phase dependent changes of the lasing intensity. A piezo positioner was used to displace the interferometer with known frequency and amplitude as a basis for real-time calibration of the interferometer's sensitivity. The signal-processing algorithm is described that allows measurements in presence of high amplitude noise leading to variation of the interferometer's operating point. Measurements of sound-induced basilar membrane displacements were made in the intact cochleae of rodents by focusing the laser beam of the interferometer through the transparent round window membrane. The interferometer provides a viable means for making subnanometre mechanical measurements from structures in the inner ears of small mammals, where opening of the cochlea is not practicable.

Algorithms↗

PubMed2005

Dependence of the DPOAE amplitude pattern on acoustical biasing of the cochlear partition.

Distortion product otoacoustic emissions (DPOAEs) were recorded from guinea pigs in response to simultaneous increases in the levels of high frequency primary tones in the presence of a low frequency biasing tone of 30 Hz at 120 dB SPL. The DPOAE amplitudes plotted as functions of the biasing tone phase angle show distinctive repeatable minima, which are identical to the amplitude notches observed for the distortion products at the output of a single saturating non-linearity. The number of the amplitude minima grows with increasing order of the DPOAE, a feature that is also reproduced by the model. The model of DPOAE generation due to a single saturating non-linearity does not explain the experimentally observed asymmetry of the response of the DPOAEs to rising and falling half cycles of the biasing tone. This asymmetry is attributed to a hypothetical mechanism, which adjusts the operating point of the outer hair cell's mechanoelectrical transducer. Experimental data were consistent with a hypothesis that, for the parameters of stimulation used in this study, both lower and upper sideband DPOAEs are dominated by emission generated from a single and spatially localized place in the cochlea.

Acoustic Stimulation↗

PubMed2003

Role of the tectorial membrane revealed by otoacoustic emissions recorded from wild-type and transgenic Tecta(deltaENT/deltaENT) mice.

Distortion product otoacoustic emissions (DPOAE) were recorded from wild-type mice and mutant Tecta(deltaENT/deltaENT) mice with detached tectorial membranes (TM) under combined ketamine/xylaxine anesthesia. In Tecta(deltaENT/deltaENT) mice, DPOAEs could be detected above the noise floor only when the levels of the primary tones exceeded 65 dB SPL. DPOAE amplitude decreased with increasing frequency of the primaries in Tecta(deltaENT/deltaENT) mice. This was attributed to hair cell excitation via viscous coupling to the surrounding fluid and not by interaction with the TM as in the wild-type mice. Local minima and corresponding phase transitions in the DPOAE growth functions occurred at higher DPOAE levels in wild-type than in Tecta(deltaENT/deltaENT) mice. In less-sensitive Tecta(deltaENT/deltaENT) mice, the position of the local minima varied nonsystematically with frequency or no minima were observed. A bell-like dependence of the DPOAE amplitude on the ratio of the primaries was recorded in both wild-type and Tecta(deltaENT/deltaENT) mice. However, the pattern of this dependence was different in the wild-type and Tecta(deltaENT/deltaENT) mice, an indication that the bell-like shape of the DPOAE was produced by a combination of different mechanisms. A nonlinear low-frequency resonance, revealed by nonmonotonicity of the phase behavior, was seen in the wild-type but not in Tecta(deltaENT/deltaENT) mice.

Acoustic Stimulation↗

PubMed2003

A second, low-frequency mode of vibration in the intact mammalian cochlea.

The mammalian cochlea is a structure comprising a number of components connected by elastic elements. A mechanical system of this kind is expected to have multiple normal modes of oscillation and associated resonances. The guinea pig cochlear mechanics was probed using distortion components generated in the cochlea close to the place of overlap between two tones presented simultaneously. Otoacoustic emissions at frequencies of the distortion components were recorded in the ear canal. The phase behavior of the emissions reveals the presence of a nonlinear resonance at a frequency about a half octave below that of the high-frequency primary tone. The location of the resonance is level dependent and the resonance shifts to lower frequencies with increasing stimulus intensity. This resonance is thought to be associated with the tectorial membrane. The resonance tends to minimize input to the cochlear receptor cells at frequencies below the high-frequency primary and increases the dynamic load to the stereocilia of the receptor cells at the primary frequency when the tectorial membrane and reticular lamina move in counterphase.

Acoustic Stimulation↗

PubMed2002

One source for distortion product otoacoustic emissions generated by low- and high-level primaries.

Distortion product otoacoustic emissions (DPOAE) elicited by tones below 60-70 dB sound pressure level (SPL) are significantly more sensitive to cochlear insults. The vulnerable, low-level DPOAE have been associated with the postulated active cochlear process, whereas the relatively robust high-level DPOAE component has been attributed to the passive, nonlinear macromechanical properties of the cochlea. However, it is proposed that the differences in the vulnerability of DPOAEs to high and low SPLs is a natural consequence of the way the cochlea responds to high and low SPLs. An active process boosts the basilar membrane (BM) vibrations, which are attenuated when the active process is impaired. However, at high SPLs the contribution of the active process to BM vibration is small compared with the dominating passive mechanical properties of the BM. Consequently, reduction of active cochlear amplification will have greatest effect on BM vibrations and DPOAEs at low SPLs. To distinguish between the "two sources" and the "single source" hypotheses we analyzed the level dependence of the notch and corresponding phase discontinuity in plots of DPOAE magnitude and phase as functions of the level of the primaries. In experiments where furosemide was used to reduce cochlear amplification, an upward shift of the notch supports the conclusion that both the low- and high-level DPOAEs are generated by a single source, namely a nonlinear amplifier with saturating I/O characteristic.

Animals↗

PubMed2002

Modifications of a single saturating non-linearity account for post-onset changes in 2f1-f2 distortion product otoacoustic emission.

2f1-f2 distortion product otoacoustic emissions (DPOAEs) were recorded from guinea pigs. DPOAEs showed complex time dependence at the onset of stimulation. The DPOAE, measured during the first 500 ms, can either decrease or increase at the onset depending on both the frequencies and levels of the primary tones. These changes are closely associated with amplitude minima (notches) of the DPOAE I/O functions. These notches are characteristic of DPOAE growth functions measured from guinea pigs for primary tones of 50-60-dB sound-pressure level (SPL). Apparent changes in the DPOAE amplitude occur because the notch shifts to higher levels of the primaries during the onset of stimulation. This shift of the notch to higher levels increases for lower f2/f1 ratios but does not exceed about 2 dB. DPOAE amplitude increases for a constant level of the primaries if the onset emission is situated at the low-level, falling slope of the notch. If the onset DPOAE is located on the high-level, rising slope of the notch, then the upward shift of the notch causes the emission either to decrease monotonically, or to decrease initially and then increase. By establishing that the 2f1-f2 onset changes reflect a shift in the growth-function notch, it is possible to predict the temporal behavior of DPOAEs in the two-dimensional space of the amplitude of the primaries and for their different frequency ratios.

Animals↗