Responses of Cat Auditory Nerve Fibers to Biphasic Electrical Current Pulses

Discharge patterns of single auditory nerve fibers were recorded from normal-hearing cats implanted with a 12-band intracochlear electrode array. Stimuli were biphasic current pulses of specifiable width, amplitude, and rate. Acoustic tuning curves were obtained to determine the cochlear positions of the fibers. Response latencies to electrical stimuli formed two groups. Short latency (0.3 to 0.7 ms) responses were attributed to direct activation of spiral ganglion neurons. At high stimulus intensities, these often exhibited abrupt shifts toward even shorter latencies. Long latency (> 1.5 ms) responses were probably caused by electrophonic activation of functional hair cells. Response thresholds to electrical stimuli depended on a fiber's proximity to the stimulating electrodes, and they did not depend on a fiber's acoustic response threshold or spontaneous discharge rate. High intensity (> 1.5 mA) stimuli could excite fibers over a wide range of characteristic frequencies, even for the narrowest (0.45 mm) electrode separations. Response threshold was an exponentially decreasing function of pulse width for widths up to 300 μs/phase. Fiber discharges were highly phase-locked at all suprathreshold intensities, and saturation discharge rates usually equaled stimulus pulse rates for rates up to at least 800 pulses/s. Dynamic ranges were small (1 to 6 dB), increased with pulse rate, and were uncorrelated with electrical response threshold. Within the dynamic range, shapes of poststimulus time and interspike interval histograms resembled those obtained in response to acoustic stimuli. Depolarization block caused fiber activity to cease in 2 to 5 seconds for sustained stimuli presented at high (> 600 pulses/s) pulse rates and intensities.

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Spatiotemporal Developmental Upregulation of Prestin Correlates With the Severity and Location of Cyclodextrin-Induced Outer Hair Cell Loss and Hearing Loss

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.643709 ◽

2021 ◽

Vol 9 ◽

Author(s):

Dalian Ding ◽

Haiyan Jiang ◽

Senthilvelan Manohar ◽

Xiaopeng Liu ◽

Li Li ◽

...

Keyword(s):

Hearing Loss ◽

Hair Cells ◽

Auditory Nerve ◽

High Frequency ◽

Spiral Ganglion ◽

Low Frequency ◽

Nerve Fibers ◽

Spiral Ganglion Neurons ◽

Auditory Nerve Fibers ◽

Ganglion Neurons

2-Hyroxypropyl-beta-cyclodextrin (HPβCD) is being used to treat Niemann-Pick C1, a fatal neurodegenerative disease caused by abnormal cholesterol metabolism. HPβCD slows disease progression, but unfortunately causes severe, rapid onset hearing loss by destroying the outer hair cells (OHC). HPβCD-induced damage is believed to be related to the expression of prestin in OHCs. Because prestin is postnatally upregulated from the cochlear base toward the apex, we hypothesized that HPβCD ototoxicity would spread from the high-frequency base toward the low-frequency apex of the cochlea. Consistent with this hypothesis, cochlear hearing impairments and OHC loss rapidly spread from the high-frequency base toward the low-frequency apex of the cochlea when HPβCD administration shifted from postnatal day 3 (P3) to P28. HPβCD-induced histopathologies were initially confined to the OHCs, but between 4- and 6-weeks post-treatment, there was an unexpected, rapid and massive expansion of the lesion to include most inner hair cells (IHC), pillar cells (PC), peripheral auditory nerve fibers, and spiral ganglion neurons at location where OHCs were missing. The magnitude and spatial extent of HPβCD-induced OHC death was tightly correlated with the postnatal day when HPβCD was administered which coincided with the spatiotemporal upregulation of prestin in OHCs. A second, massive wave of degeneration involving IHCs, PC, auditory nerve fibers and spiral ganglion neurons abruptly emerged 4–6 weeks post-HPβCD treatment. This secondary wave of degeneration combined with the initial OHC loss results in a profound, irreversible hearing loss.

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Frequency extent of two-tone facilitation in onset units in the ventral cochlear nucleus

Journal of Neurophysiology ◽

10.1152/jn.1996.75.1.380 ◽

1996 ◽

Vol 75 (1) ◽

pp. 380-395 ◽

Cited By ~ 46

Author(s):

D. Jiang ◽

A. R. Palmer ◽

I. M. Winter

Keyword(s):

Cochlear Nucleus ◽

Auditory Nerve ◽

Low Frequency ◽

Nerve Fibers ◽

Inhibitory Input ◽

Ventral Cochlear Nucleus ◽

Narrow Region ◽

Morphological Studies ◽

Wide Range ◽

Auditory Nerve Fibers

1. The frequency threshold curves (FTCs) of 91 single units in the cochlear nucleus of the anesthetized guinea pig were measured using a conventional single-tone paradigm and a two-tone paradigm designed to elucidate the frequency extent of two-tone facilitation in onset units (On). Units were classified according to existing classification schemes into primary-like (n = 3), chopper (n = 23), and three onset groups: OnI (n = 12), OnC (n = 29), and OnL (n = 24). Histological reconstructions show onset units to be widely distributed within the ventral cochlear nucleus in a manner generally consistent with its tonotopic organization. 2. The FTCs of onset units differed in their minimum thresholds, the steepness of their high- and low-frequency cutoffs, and their sharpness of tuning as quantified by the quality factor at 10 dB (Q10dB) above best frequency (BF) threshold values. There was considerable overlap in the sharpness of tuning between onset units and auditory nerve fibers, as indicated by the distribution of Q10dB values in the octave around 10 kHz: onset units had Q10dB values of 3.56 +/- 1.38 (SD), compared with 6.3 +/- 2.48 for auditory nerve fibers. The tuning of chopper units was similar to that of auditory nerve fibers (5.52 +/- 1.46). 3. Seventy-five percent of onset units showed some degree of facilitation (a threshold reduction) when their FTCs were measured in the presence of BF tones 4 dB below BF threshold. The frequency extent of such facilitation was variable, with a maximum of 6 octaves around the BF. In extreme cases facilitation could be measured when the BF tone was as low as 30 dB below BF threshold. 4. In 17% of onset units, suppressive effects were evident, as shown by noncontiguous frequency regions of facilitation. These suppressive effects might be a reflection either of suppression in the auditory nerve input or of a direct inhibitory input to the onset units. The strength of this effect suggests that inhibition is a likely explanation, consistent with the finding in previous morphological studies of profuse synapses with pleomorphic vesicles on multipolar cells. 5. FTCs of chopper and primary-like units measured in the presence of BF tones showed little facilitation. The facilitation that was observed in chopper units was confined to a narrow region around BF and disappeared when the facilitatory tone was lowered to 4 dB below BF threshold. 6. These data support the hypothesis that onset units, but not chopper or primary-like units, receive excitatory inputs from auditory nerve fibers with a wide range of BFs. However, the frequency range of facilitation and the magnitude of the threshold facilitation varied from unit to unit, suggesting that the off-BF inputs from auditory nerve fibers are not evenly distributed or equally effective in all units.

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Neural encoding of single-formant stimuli in the cat. I. Responses of auditory nerve fibers

Journal of Neurophysiology ◽

10.1152/jn.1993.70.3.1054 ◽

1993 ◽

Vol 70 (3) ◽

pp. 1054-1075 ◽

Cited By ~ 24

Author(s):

X. Wang ◽

M. B. Sachs

Keyword(s):

Direct Current ◽

Auditory Nerve ◽

Nerve Fibers ◽

Fundamental Component ◽

Sound Levels ◽

Wide Range ◽

Spectral Components ◽

Auditory Nerve Fibers ◽

High Sound ◽

Envelope Modulation

1. We have studied auditory responses to a set of speech-related narrowband sounds, single-formant stimuli (SFSs), in populations of auditory nerve fibers (ANFs). An analytic method was developed to extract the envelope of temporal discharge patterns of the ANF responses to nonsinusoidally modulated stimuli, whose spectra have multiple clusters of components. Such responses are often encountered in the auditory system when complex stimuli are used and have traditionally been studied by analyzing the fundamental component of the responses. 2. The envelope modulation in the SFSs is shown to be represented by the response patterns of ANFs. When the whole ANF population is considered, the information on modulation in stimulus envelope does not disappear at the highest sound level tested at all best frequencies (BFs) we studied (1-10 kHz). The representation is the best at medium sound levels and degrades at high sound levels. Low/medium-spontaneous rate (SR) ANFs showed greater envelope modulation in their responses at high sound levels than do high-SR ANFs. The quality of the representation at high sound levels is, on average, proportional to BF threshold of an ANF. On the basis of populations of ANFs with all SRs, the envelope modulation in the SFSs is represented over a wide range of sound levels. 3. We found that low-BF ANFs differ from high-BF ANFs in representing envelope modulation in the SFSs. For ANFs with BFs less than approximately 6 kHz, information on stimulus envelope is not only contained in spectral components near direct current but also in components at the vicinities of frequencies equal to BF and its multiples. In fact, for ANFs with BFs < 3 kHz, the contribution from spectral components centered at BF to overall response modulation is greater than that from spectral components near direct current. These findings indicate that, by using measures solely based on the fundamental component, the amount of modulation in the responses to narrowband stimuli is underestimated for low-BF ANFs. 4. Off-BF stimulation of ANFs with SFSs was found to result in increased envelope modulation in responses at high sound levels. The further away the stimulus is centered relative to unit BF, the greater the modulation it induces, provided that the stimulus is capable of exciting the unit. An SFS centered as close as 15% off unit BF can produce a significant increase in the modulation of responses at very high sound levels.(ABSTRACT TRUNCATED AT 400 WORDS)

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