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

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.

Acoustic reflex frequency selectivity in single stapedius motoneurons of the cat

1992 ◽  
Vol 68 (3) ◽  
pp. 807-817 ◽  
Author(s):  
J. B. Kobler ◽  
J. J. Guinan ◽  
S. R. Vacher ◽  
B. E. Norris
Keyword(s):  
Auditory Nerve ◽  
High Frequency ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Main Function ◽  
Acoustic Reflex ◽  
Tuning Curves ◽  
Acoustic Reflexes ◽  
Auditory Nerve Fibers ◽  
Decerebrate Cats

1. The sound frequency selectivities of single stapedius motoneurons were investigated in ketamine anesthetized and in decerebrate cats by recording from axons in the small nerve fascicles entering the stapedius muscle. 2. Stapedius motoneuron tuning curves (TCs) were very broad, similar to the tuning of the overall acoustic reflexes as determined by electromyographic recordings. The lowest thresholds were usually for sound frequencies between 1 and 2 kHz, although many TCs also had a second sensitive region in the 6- to 12-kHz range. The broad tuning of stapedius motoneurons implies that inputs derived from different cochlear frequency regions (which are narrowly tuned) must converge at a point central to the stapedius motoneuron outputs, possibly at the motoneuron somata. 3. There were only small differences in tuning among the four previously described groups of stapedius motoneurons categorized by sensitivity to ipsilateral and contralateral sound. The gradation in high-frequency versus low-frequency sensitivity across motoneurons suggests there are not distinct subgroups of stapedius motoneurons, based on their TCs. 4. The thresholds and shapes of stapedius motoneuron TCs support the hypothesis that the stapedius acoustic reflex is triggered by summed activity of low-spontaneous-rate auditory nerve fibers with both low and high characteristic frequencies (CFs). Excitation of high-CF auditory nerve fibers by sound in their TC “tails” is probably an important factor in eliciting the reflex. 5. In general, the most sensitive frequency for stapedius motoneurons is higher than the frequency at which stapedius contractions produce the greatest attenuation of middle ear transmission. We argue that this is true because the main function of the stapedius acoustic reflex is to reduce the masking of responses to high-frequency sounds produced by low-frequency sounds.

scholarly journals Phase Locking of Auditory-Nerve Fibers to the Envelopes of High-Frequency Sounds: Implications for Sound Localization

2006 ◽  
Vol 96 (5) ◽  
pp. 2327-2341 ◽  
Author(s):  
Anna Dreyer ◽  
Bertrand Delgutte
Keyword(s):  
Auditory Nerve ◽  
High Frequency ◽  
Phase Locking ◽  
Discrimination Performance ◽  
Nerve Fibers ◽  
Spontaneous Discharge ◽  
Neurophysiological Studies ◽  
Pure Tones ◽  
Auditory Nerve Fibers ◽  
Psychophysical Studies

Although listeners are sensitive to interaural time differences (ITDs) in the envelope of high-frequency sounds, both ITD discrimination performance and the extent of lateralization are poorer for high-frequency sinusoidally amplitude-modulated (SAM) tones than for low-frequency pure tones. Psychophysical studies have shown that ITD discrimination at high frequencies can be improved by using novel transposed-tone stimuli, formed by modulating a high-frequency carrier by a half-wave–rectified sinusoid. Transposed tones are designed to produce the same temporal discharge patterns in high-characteristic frequency (CF) neurons as occur in low-CF neurons for pure-tone stimuli. To directly test this hypothesis, we compared responses of auditory-nerve fibers in anesthetized cats to pure tones, SAM tones, and transposed tones. Phase locking was characterized using both the synchronization index and autocorrelograms. With both measures, phase locking was better for transposed tones than for SAM tones, consistent with the rationale for using transposed tones. However, phase locking to transposed tones and that to pure tones were comparable only when all three conditions were met: stimulus levels near thresholds, low modulation frequencies (<250 Hz), and low spontaneous discharge rates. In particular, phase locking to both SAM tones and transposed tones substantially degraded with increasing stimulus level, while remaining more stable for pure tones. These results suggest caution in assuming a close similarity between temporal patterns of peripheral activity produced by transposed tones and pure tones in both psychophysical studies and neurophysiological studies of central neurons.

Responses of auditory‐nerve fibers to multiple‐tone complexes

1987 ◽  
Vol 82 (6) ◽  
pp. 1989-2000 ◽  
Author(s):  
Li Deng ◽  
C. Daniel Geisler ◽  
Steven Greenberg
Keyword(s):  
Auditory Nerve ◽  
Nerve Fibers ◽  
Auditory Nerve Fibers

Encoding timing and intensity in the ventral cochlear nucleus of the cat

1986 ◽  
Vol 56 (2) ◽  
pp. 261-286 ◽  
Author(s):  
W. S. Rhode ◽  
P. H. Smith
Keyword(s):  
Firing Rate ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Cell Types ◽  
Nerve Fibers ◽  
Frequency Selectivity ◽  
Firing Rates ◽  
Ventral Cochlear Nucleus ◽  
Auditory Nerve Fibers ◽  
Different Cell Types

Physiological response properties of neurons in the ventral cochlear nucleus have a variety of features that are substantially different from the stereotypical auditory nerve responses that serve as the principal source of activation for these neurons. These emergent features are the result of the varying distribution of auditory nerve inputs on the soma and dendrites of the various cell types within the nucleus; the intrinsic membrane characteristics of the various cell types causing different responses to the same input in different cell types; and secondary excitatory and inhibitory inputs to different cell types. Well-isolated units were recorded with high-impedance glass microelectrodes, both intracellularly and extracellularly. Units were characterized by their temporal response to short tones, rate vs. intensity relation, and response areas. The principal response patterns were onset, chopper, and primary-like. Onset units are characterized by a well-timed first spike in response to tones at the characteristic frequency. For frequencies less than 1 kHz, onset units can entrain to the stimulus frequency with greater precision than their auditory nerve inputs. This implies that onset units receive converging inputs from a number of auditory nerve fibers. Onset units are divided into three subcategories, OC, OL, and OI. OC units have extraordinarily wide dynamic ranges and low-frequency selectivity. Some are capable of sustaining firing rates of 800 spikes/s at high intensities. They have the smallest standard deviation and coefficient of variation of the first spike latency of any cells in the cochlear nuclei. OC units are candidates for encoding intensity. OI and OL units differ from OC units in that they have dynamic ranges and frequency selectivity ranges much like those of auditory nerve fibers. They differ from one another in their steady-state firing rates; OI units fire mainly at the onset of a tone. OI units also differ from OL units in that they prefer frequency sweeps in the low to high direction. Primary-like-with-notch (PLN) units also respond to tones with a well-timed first spike. They differ from onset cells in that the onset peak is not always as precise as the spontaneous rate is higher. A comparison of spontaneous firing rate and saturation firing rate of PLN units with auditory nerve fibers suggest that PLN units receive one to four auditory nerve fiber inputs. Chopper units fire in a sustained regular manner when they are excited by sound.(ABSTRACT TRUNCATED AT 400 WORDS)

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