Inner Hair Cell Responses Research Articles

Effects of sensorineural hearing loss on formant-frequency discrimination: Measurements and models

This study concerns the effect of hearing loss on discrimination of formant frequencies in vowels. In the response of the healthy ear to a harmonic sound, auditory-nerve (AN) rate functions fluctuate at the fundamental frequency, F0. Responses of inner-hair-cells (IHCs) tuned near spectral peaks are captured (or dominated) by a single harmonic, resulting in lower fluctuation depths than responses of IHCs tuned between spectral peaks. Therefore, the depth of neural fluctuations (NFs) varies along the tonotopic axis and encodes spectral peaks, including formant frequencies of vowels. This NF code is robust across a wide range of sound levels and in background noise. The NF profile is converted into a rate-place representation in the auditory midbrain, wherein neurons are sensitive to low-frequency fluctuations. The NF code is vulnerable to sensorineural hearing loss (SNHL) because capture depends upon saturation of IHCs, and thus the interaction of cochlear gain with IHC transduction. In this study, formant-frequency discrimination limens (DLFFs) were estimated for listeners with normal hearing or mild to moderate SNHL. The F0 was fixed at 100 Hz, and formant peaks were either aligned with harmonic frequencies or placed between harmonics. Formant peak frequencies were 600 and 2000 Hz, in the range of first and second formants of several vowels. The difficulty of the task was varied by changing formant bandwidth to modulate the contrast in the NF profile. Results were compared to predictions from model auditory-nerve and inferior colliculus (IC) neurons, with listeners’ audiograms used to individualize the AN model. Correlations between DLFFs, audiometric thresholds near the formant frequencies, age, and scores on the Quick speech-in-noise test are reported. SNHL had a strong effect on DLFF for the second formant frequency (F2), but relatively small effect on DLFF for the first formant (F1). The IC model appropriately predicted substantial threshold elevations for changes in F2 as a function of SNHL and little effect of SNHL on thresholds for changes in F1.

Modulation masking produced by a low-frequency pure tone

An intense low-frequency tone can affect the perception of amplitude modulation (AM) applied to a high-frequency carrier. Here, thresholds for detecting AM of a 3000-Hz carrier were measured in the presence of a 50-Hz pure tone at 91 dB SPL. When the carrier was presented at 20 dB sensation level (SL), the thresholds were higher than in the absence of the 50-Hz tone, increased when the AM frequency was increased from 20 to 100 Hz, and did not show a maximum near 50 Hz, as would be expected if the effect of the 50-Hz tone resulted from modulation detection interference. When the AM frequency was fixed at 50 Hz, the AM detection thresholds showed a minimum when the phase of the AM was 90° ahead of the phase of the 50-Hz tone (denoted Δφ = 90°) and a maximum for Δφ = 270°. To assess the role of the outer hair cells (OHCs), AM detection thresholds were measured as a function of Δφ using SLs of 20 and 50 dB for normal-hearing participants and 20 dB for hearing-impaired participants. It was assumed that the latter would have impaired OHC function. The pattern of the results was similar across SLs and groups: AM detection thresholds were 8–10 dB lower for Δφ = 90° than for Δφ = 270° in all cases. This suggests that the OHCs do not play a large role in these effects and supports the idea that the low-frequency tone biases the responses of inner hair cells tuned to high frequencies.

The Role of BKCa Channels in Electrical Signal Encoding in the Mammalian Auditory Periphery

Large-conductance voltage- and Ca(2+)-activated K+ channels (BKCa) are involved in shaping spiking patterns in many neurons. Less is known about their role in mammalian inner hair cells (IHCs), mechanosensory cells with unusually large BKCa currents. These currents may be involved in shaping the receptor potential, implying crucial importance for the properties of afferent auditory signals. We addressed the function of BKCa by recording sound-induced responses of afferent auditory nerve (AN) fibers from mice with a targeted deletion of the pore-forming alpha-subunit of BKCa (BKalpha(-/-)) and comparing these with voltage responses of current-clamped IHCs. BKCa-mediated currents in IHCs were selectively abolished in BKalpha(-/-), whereas cochlear physiology was essentially normal with respect to cochlear sensitivity and frequency tuning.BKalpha(-/-) AN fibers showed deteriorated precision of spike timing, measured as an increased variance of first spike latency in response to tone bursts. This impairment could be explained by a slowed voltage response in the presynaptic IHC resulting from the reduced K+ conductance in the absence of BKCa. Maximum spike rates of AN fibers were reduced nearly twofold in BKalpha(-/-), contrasting with increased voltage responses of IHCs. In addition to presynaptic changes, which may be secondary to a modest depolarization of BKalpha(-/-) IHCs, this reduction in AN rates suggests a role of BKCa in postsynaptic AN neurons, which was supported by increased refractory periods. In summary, our results indicate an essential role of IHC BKCa channels for precise timing of high-frequency cochlear signaling as well as a function of BKCa in the primary afferent neuron.

Cochlear mechanisms of frequency and intensity coding. I. The place code for pitch

In the past, several researchers have reported a substantial shift in the peak of the tone-evoked excitation pattern toward the base of the cochlea following an increase in the SPL of the stimulating tone. Evidence for such peak shifts has been found in the responses of auditory nerve fibers, cochlear microphonics, and the responses of outer hair cells and supporting cells in the cochlea, as well as in basilar membrane vibration measurements, and indirectly, in psychophysical data. However, direct evidence for such a peak shift in inner hair cell (IHC) responses has been relatively sparse. If the peak shift is preserved in the information conveyed to the auditory nerve fibers by the IHCs, the classical `place theory' for frequency coding in the cochlea requires modification. In this study, the nature and extent of the SPL-dependent peak shift is examined with the help of recordings in the IHCs and other cells of the organ of Corti in the 0.5–2.5 kHz region of the Mongolian gerbil cochlea. It is demonstrated that the peak shift is a universal phenomenon in the diverse cell types in this region of the cochlea. Most importantly, a large SPL-dependent peak shift is demonstrated in IHC responses. On the other hand, the recordings indicate that the apical cutoff of the spatial excitation pattern is SPL-independent. We conclude, therefore, that the place theory of pitch perception must be abandoned or at least modified.

Two-tone suppression in inner hair cell responses: Correlates of rate suppression in the auditory nerve

Inner hair cell (IHC) recordings were made from second turn of the guinea pig cochlea where characteristic frequencies are approximately 4000 Hz. In order to compare IHC responses with rate suppression measured in the auditory nerve, suppressors were introduced that produced little or no response in the hair cell. The effects of a variable-frequency suppressor on a constant-frequency probe, placed near characteristic frequency, were also investigated since this paradigm is commonly used in single unit experiments. Resulting magnitude changes were measured in the fundamental component of the ac receptor potential and/or in the total de produced in the region of temporal overlap between the two stimulus inputs. This latter component is escecially important when considering how changes in IHC responses relate to decreases in discharge rate in single auditorynnerve fibers. Since the ac receptor potential is filtered by the hair cell's basolateral membrane, the dc component probably controls transmitter release at the characteristic frequency of these second-turn IHCs. Based on results from these and previous experiments, a proposal is advanced to explain the evolution of two-tone suppression in the peripheral auditory system. The paper also discusses the use of excitatory versus non-excitatory suppressors and includes a description of two-tone suppression areas at the mechanical, IHC and single unit levels. The explanation of low-side suppression areas is of special interest since hitherto they have been difficult to model (Kim, 1985).

Intracellular recordings from supporting cells in the guinea pig cochlea: DC potentials

1. Supporting cells and hair cells from the low-frequency region of the guinea pig cochlea were studied in vivo using intracellular recording and horseradish-peroxidase (HRP) marking techniques. 2. The response of third- and fourth-turn support cells to tone bursts is composed of a number of components: an AC component at the frequency of the stimulating tone, harmonic components, a DC component present at the onset of the stimulating tone (the early DC), a slowly developing depolarization, and a slowly decaying afterpotential. 3. The early DC of support-cell responses is generally less than or equal to that in the adjacent organ of Corti fluids [at the best frequency (BF) for an 80 or 90 dB sound pressure level (SPL) stimulus the average early DC of support-cell responses is 0.9 times that of the adjacent fluids; n = 71], and both are less than that seen in the hair cells [average early DC of inner hair-cell (IHC) responses at the same sound levels is 14.2 times that in the adjacent organ fluids, n = 15; average early DC of outer hair-cell (OHC) responses is 11.5 times that in nearby organ fluids, n = 2)]. 4. The end DC, magnitude of the DC response shortly before signal end, in responses of support cells deep into Corti's organ [e.g., pillar, inner phalangeal, border cells] is often greater than that recorded in the potentials of the adjacent organ fluids (e.g., for an 80 or 90 dB SPL stimulus at the BF with a 30 ms steady-state time, the average end DC of the support cells deep into the organ is 2 times that of the adjacent organ fluids, n = 42). In contrast, the end DC for the responses of peripheral support cells--the Hensen's cells--generally equals, or is smaller than, the extracellular-fluid counterpart (for an 80 or 90 dB SPL stimulus, the average end DC of Hensen's cells is 0.9 times that of the nearby, outer-tunnel fluids, n = 29). Thus a difference exists across support-cell type with respect to support-cell end DC vis-à-vis that of the adjacent organ of Corti fluids. 5. A slowly increasing depolarization is often present in moderate and high-level support-cell responses. It is not normally present in IHC or OHC responses. Magnitude of the slowly increasing depolarization, the slow DC, is dependent on stimulus duration and stimulus level.(ABSTRACT TRUNCATED AT 400 WORDS)

Low-frequency responses of inner hair cells: evidence for a mechanical origin of peak splitting

Auditory nerve fibres usually respond to a preferred phase of a low frequency sinusoidal stimulus. However, at high sound pressures fibres may either change the preferred phase of response or respond to more than one phase of the stimulus. This complex firing pattern is known as peak splitting. Hypotheses for the origin of peak splitting have ranged from micromechanical models to models incorporating electrical interactions between inner and outer hair cells. In order to determine the origin of peak splitting, the potential across the IHC synaptic membrane has been measured during stimulation with low frequency tones and it is found that the IHC receptor potentials exhibit peak splitting at sound pressures that coincide with the saturation of the outer hair cell receptor potentials. Current injection experiments show that peak splitting is also recorded in the resistance change of the inner hair cell during acoustic stimulation. It is concluded from this evidence that peak splitting is present in the mechanical input to the IHC.

Measurement of low-frequency receptor potentials in inner hair cells: a theoretical analysis

The measurement of the low-frequency responses of inner hair cells is complicated by the fact that extracellular cochlear microphonic may be larger than the intracellular inner hair cell potential. A subtraction technique is proposed in which the extracellular and intracellular potentials are recorded sequentially and then subtracted to give an estimate of the true membrane potential. A theoretical analysis is presented which predicts that this calculated inner hair cell membrane potential is a more accurate measure of inner hair cell receptor current than the membrane potential measured with respect to a remote indifferent electrode.

The morphology and physiology of hair cells in organotypic cultures of the mouse cochlea

Organotypic explant cultures were prepared from the cochleas of 1 to 3 day post-natal mice and maintained in vitro for up to 5 days. The hair cells retain morphological integrity for the duration of the culture period although they exhibit embryological features such as a kinocilium and additional microvilli on their apical surfaces. The resting membrane potentials of mouse inner hair cells (IHCs) in vitro are similar to those of guinea-pig IHCs in vivo but the membrane potentials of outer hair cells (OHCs) in the mouse cochlea in vitro are less polarized than the resting membrane potentials of OHCs in the basal turn of the guinea-pig cochlea in vivo. The voltage responses of IHCs and OHCs to sinusoidal displacements of their stereocilia are similar to each other in waveform and dynamic range, although the responses of IHCs are larger than those of OHCs. The relationship between transducer conductance and stereocilia displacement in IHCs and OHCs is non-linear and largely accounts for the depolarizing asymmetry of the voltage response. The receptor potentials of IHCs and OHCs reverse close to 0 mV indicating that the transducer conductance is non-selective for cations. The voltage responses of IHCs and OHCs to intracellular current injection rectify when the membrane potentials are more depolarized than about − 30 mV. This rectification is most pronounced in OHCs. OHCs also exhibit a time-dependent, voltage-sensitive conductance although they do not behave as electrical resonators.

The responses of inner hair cells to basilar membrane velocity during low frequency auditory stimulation in the guinea pig cochlea

Intracellular receptor potentials were recorded from inner hair cells in the basal turn of the guinea pig cochlea in response to low frequency tones. These were compared with the cochlear microphonic (CM) recorded from the scala tympani and sound pressure at the tympanic membrane. The CM is symmetrical and behaves as if it responds to basilar membrane displacement. The depolarizing phase of the inner hair cell receptor potential exceeds the hyperpolarizing phase with a ratio of about 3 : 1 in response to sinusoidal stimulation. Below 100 Hz inner hair cell receptor potentials phase lead sound pressure by 180° and their amplitudes increase at a rate of 12 dB/octave. Above 200 Hz their receptor potentials are in phase with CM. The capacitative impedances of the hair cells delay and attenuate the intracellular receptor potentials at frequencies above 178–873 Hz. We conclude that CM is dominated by the responses of outer hair cells, and that at frequencies below 100–200 Hz inner hair cells respond to basilar membrane velocity. Above this they respond to basilar membrane displacement.

Biophysics and physiology of the inner ear.

Biophysics and physiology of the inner ear.