Auditory-Nerve Responses in Mice with Noise-Induced Cochlear Synaptopathy

2021 ◽  
Author(s):  
Kirupa Suthakar ◽  
M. Charles Liberman
Keyword(s):  
Auditory Nerve ◽  
Guinea Pigs ◽  
Frequency Tuning ◽  
Tone Burst ◽  
Nerve Fibers ◽  
Ribbon Synapses ◽  
Age Related ◽  
Synaptic Markers ◽  
Basal Half ◽  
Masking Noise

Cochlear synaptopathy is the noise-induced or age-related loss of ribbon synapses between inner hair cells (IHCs) and auditory nerve fibers (ANFs), first reported in CBA/CaJ mice. Recordings from single ANFs in anaesthesized, noise-exposed guinea pigs suggested that neurons with low spontaneous rates (SRs) and high thresholds are more vulnerable than low-threshold, high-SR fibers. However, there is extensive post-exposure regeneration of ANFs in guinea pigs, but not in mice. Here, we exposed CBA/CaJ mice to octave-band noise and recorded sound-evoked and spontaneous activity from single ANFs at least 2 weeks later. Confocal analysis of cochleae immunostained for pre- and post-synaptic markers confirmed the expected loss of 40 - 50% of ANF synapses in the basal half of the cochlea, however, our data were not consistent with a selective loss of low-SR fibers. Rather they suggested a loss of both SR groups in synaptopathic regions. Single-fiber thresholds and frequency tuning recovered to pre-exposure levels however, response to tone bursts showed increased peak and steady-state firing rates as well as decreased jitter in first-spike latencies. This apparent gain-of-function increased the robustness of tone-burst responses in the presence of continuous masking noise. This study suggests that the nature of noise-induced synaptic damage varies between different species and that, in mouse, the noise-induced hyperexcitability seen in central auditory circuits is also observed at the level of the auditory nerve.

scholarly journals Synaptic migration and reorganization after noise exposure suggests regeneration in a mature mammalian cochlea

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Tyler T. Hickman ◽  
Ken Hashimoto ◽  
Leslie D. Liberman ◽  
M. Charles Liberman
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Auditory Nerve ◽  
Guinea Pigs ◽  
Noise Exposure ◽  
Recovery Period ◽  
Nerve Fibers ◽  
Neural Regeneration ◽  
Adult Mice ◽  
Synaptic Markers

AbstractOverexposure to intense noise can destroy the synapses between auditory nerve fibers and their hair cell targets without destroying the hair cells themselves. In adult mice, this synaptopathy is immediate and largely irreversible, whereas, in guinea pigs, counts of immunostained synaptic puncta can recover with increasing post-exposure survival. Here, we asked whether this recovery simply reflects changes in synaptic immunostaining, or whether there is actual retraction and extension of neurites and/or synaptogenesis. Analysis of the numbers, sizes and spatial distribution of pre- and post-synaptic markers on cochlear inner hair cells, in guinea pigs surviving from 1 day to 6 months after a synaptopathic exposure, shows dramatic synaptic re-organization during the recovery period in which synapse counts recover from 16 to 91% of normal in the most affected regions. Synaptic puncta move all over the hair cell membrane during recovery, translocating far from their normal positions at the basolateral pole, and auditory-nerve terminals extend towards the hair cell’s apical end to re-establish contact with them. These observations provide stronger evidence for spontaneous neural regeneration in a mature mammalian cochlea than can be inferred from synaptic counts alone.

Frequency Tuning and Spontaneous Activity in the Auditory Nerve and Cochlear Nucleus Magnocellularis of the Barn Owl Tyto alba

1997 ◽  
Vol 77 (1) ◽  
pp. 364-377 ◽  
Author(s):  
Christine Köppl
Keyword(s):  
Response Latency ◽  
Cochlear Nucleus ◽  
Auditory Nerve ◽  
Frequency Tuning ◽  
Barn Owl ◽  
Nerve Fibers ◽  
Spontaneous Discharge ◽  
Tyto Alba ◽  
Nucleus Magnocellularis ◽  
Auditory Nerve Fibers

Köppl, Christine. Frequency tuning and spontaneous activity in the auditory nerve and cochlear nucleus magnocellularis of the barn owl Tyto alba. J. Neurophysiol. 77: 364–377, 1997. Single-unit recordings were obtained from the brain stem of the barn owl at the level of entrance of the auditory nerve. Auditory nerve and nucleus magnocellularis units were distinguished by physiological criteria, with the use of the response latency to clicks, the spontaneous discharge rate, and the pattern of characteristic frequencies encountered along an electrode track. The response latency to click stimulation decreased in a logarithmic fashion with increasing characteristic frequency for both auditory nerve and nucleus magnocellularis units. The average difference between these populations was 0.4–0.55 ms. The most sensitive thresholds were ∼0 dB SPL and varied little between 0.5 and 9 kHz. Frequency-threshold curves showed the simple V shape that is typical for birds, with no indication of a low-frequency tail. Frequency selectivity increased in a gradual, power-law fashion with increasing characteristic frequency. There was no reflection of the unusual and greatly expanded mapping of higher frequencies on the basilar papilla of the owl. This observation is contrary to the equal-distance hypothesis that relates frequency selectivity to the spatial respresentation in the cochlea. On the basis of spontaneous rates and/or sensitivity there was no evidence for distinct subpopulations of auditory nerve fibers, such as the well-known type I afferent response classes in mammals. On the whole, barn owl auditory nerve physiology conformed entirely to the typical patterns seen in other bird species. The only exception was a remarkably small spread of thresholds at any one frequency, this being only 10–15 dB in individual owls. Average spontaneous rate was 72.2 spikes/s in the auditory nerve and 219.4 spikes/s for nucleus magnocellularis. This large difference, together with the known properties of endbulb-of-Held synapses, suggests a convergence of ∼2–4 auditory nerve fibers onto one nucleus magnocellularis neuron. Some auditory nerve fibers as well as nucleus magnocellularis units showed a quasiperiodic spontaneous discharge with preferred intervals in the time-interval histogram. This phenomenon was observed at frequencies as high as 4.7 kHz.

Degeneration of auditory nerve fibers in guinea pigs with severe sensorineural hearing loss

2017 ◽  
Vol 345 ◽  
pp. 79-87 ◽  
Author(s):  
Steven Kroon ◽  
Dyan Ramekers ◽  
Emma M. Smeets ◽  
Ferry G.J. Hendriksen ◽  
Sjaak F.L. Klis ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Auditory Nerve ◽  
Guinea Pigs ◽  
Nerve Fibers ◽  
Sensorineural Hearing ◽  
Auditory Nerve Fibers

scholarly journals Age-Dependent Auditory Processing Deficits after Cochlear Synaptopathy Depend on Auditory Nerve Latency and the Ability of the Brain to Recruit LTP/BDNF

2020 ◽  
Vol 10 (10) ◽  
pp. 710
Author(s):  
Philine Marchetta ◽  
Daria Savitska ◽  
Angelika Kübler ◽  
Giulia Asola ◽  
Marie Manthey ◽  
...  
Keyword(s):  
Temporal Processing ◽  
Auditory Processing ◽  
Auditory Nerve ◽  
Temporal Discrimination ◽  
Long Term Potentiation ◽  
Nerve Fibers ◽  
Age Related ◽  
Age Dependent ◽  
Processing Deficits ◽  
Neural Gain

Age-related decoupling of auditory nerve fibers from hair cells (cochlear synaptopathy) has been linked to temporal processing deficits and impaired speech recognition performance. The link between both is elusive. We have previously demonstrated that cochlear synaptopathy, if centrally compensated through enhanced input/output function (neural gain), can prevent age-dependent temporal discrimination loss. It was also found that central neural gain after acoustic trauma was linked to hippocampal long-term potentiation (LTP) and upregulation of brain-derived neurotrophic factor (BDNF). Using middle-aged and old BDNF-live-exon-visualization (BLEV) reporter mice we analyzed the specific recruitment of LTP and the activity-dependent usage of Bdnf exon-IV and -VI promoters relative to cochlear synaptopathy and central (temporal) processing. For both groups, specimens with higher or lower ability to centrally compensate diminished auditory nerve activity were found. Strikingly, low compensating mouse groups differed from high compensators by prolonged auditory nerve latency. Moreover, low compensators exhibited attenuated responses to amplitude-modulated tones, and a reduction of hippocampal LTP and Bdnf transcript levels in comparison to high compensators. These results suggest that latency of auditory nerve processing, recruitment of hippocampal LTP, and Bdnf transcription, are key factors for age-dependent auditory processing deficits, rather than cochlear synaptopathy or aging per se.

Spontaneous Activity of Auditory Nerve Fibers in the Barn Owl (Tyto alba): Analyses of Interspike Interval Distributions

2009 ◽  
Vol 101 (6) ◽  
pp. 3169-3191 ◽  
Author(s):  
Heinrich Neubauer ◽  
Christine Köppl ◽  
Peter Heil
Keyword(s):  
Spontaneous Activity ◽  
Auditory Nerve ◽  
Interspike Interval ◽  
Barn Owl ◽  
Nerve Fibers ◽  
Temporal Coding ◽  
Tyto Alba ◽  
Ribbon Synapses ◽  
Auditory Systems ◽  
The Mean

In vertebrate auditory systems, the conversion from graded receptor potentials across the hair-cell membrane into stochastic spike trains of the auditory nerve (AN) fibers is performed by ribbon synapses. The statistics underlying this process constrain auditory coding but are not precisely known. Here, we examine the distributions of interspike intervals (ISIs) from spontaneous activity of AN fibers of the barn owl ( Tyto alba), a nocturnal avian predator whose auditory system is specialized for precise temporal coding. The spontaneous activity of AN fibers, with the exception of those showing preferred intervals, is commonly thought to result from excitatory events generated by a homogeneous Poisson point process, which lead to spikes unless the fiber is refractory. We show that the ISI distributions in the owl are better explained as resulting from the action of a brief refractory period (∼0.5 ms) on excitatory events generated by a homogeneous stochastic process where the distribution of interevent intervals is a mixture of an exponential and a gamma distribution with shape factor 2, both with the same scaling parameter. The same model was previously shown to apply to AN fibers in the cat. However, the mean proportions of exponentially versus gamma-distributed intervals in the mixture were different for cat and owl. Furthermore, those proportions were constant across fibers in the cat, whereas they covaried with mean spontaneous rate and with characteristic frequency in the owl. We hypothesize that in birds, unlike in mammals, more than one ribbon may provide excitation to most fibers, accounting for the different proportions, and that variation in the number of ribbons may underlie the variation in the proportions.

Antimasking effects of the olivocochlear reflex. II. Enhancement of auditory-nerve response to masked tones

1993 ◽  
Vol 70 (6) ◽  
pp. 2533-2549 ◽  
Author(s):  
T. Kawase ◽  
B. Delgutte ◽  
M. C. Liberman
Keyword(s):  
Auditory Nerve ◽  
Dynamic Range ◽  
Detection Threshold ◽  
Tone Burst ◽  
Nerve Fibers ◽  
Burst Frequency ◽  
Continuous Response ◽  
Discharge Rates ◽  
Burst Intensity ◽  
Level Function

1. The antimasking effects of olivocochlear (OC) efferent feedback were studied in anesthetized or decerebrate cats by comparing responses of single auditory-nerve fibers (ANFs) to tone bursts in continuous masking noise seen with and without addition of a moderate-level contralateral noise known to activate the OC reflex. Responses were measured as a function of tone-burst intensity, tone-burst frequency, and masker intensity and were analyzed so as to allow quantitative estimates of the detectability of the tone bursts against the noise background. 2. Addition of the contralateral OC elicitor both increased the maximum discharge rates to the masked tone bursts and decreased the rates to the ipsilateral masker. The rate increases to the tone bursts could be explained on the basis of a decrease in adaptation caused by decreasing the steady response to the masker. The result is a steepening of the rate-versus-level function for masked tone bursts and a concomitant increase in the estimated discriminability of small increments of tone-burst intensity. 3. For tone bursts at the fiber's characteristic frequency (CF), the OC effects on detection threshold for the masked tone bursts depended on masker level, with small increases in threshold for low masker levels and somewhat larger decreases in threshold for higher masker levels. For tone bursts below CF, OC effects, when present, always decreased the detection threshold. 4. The largest antimasking effects were seen for fibers with CFs between 6 and 12 kHz and for masker levels within 20 dB of the fiber's threshold to the masker. These trends appeared to hold for fibers of all spontaneous rates (SRs). 5. Enhancement of the response to unmasked tone bursts and concomitant decrease in the “spontaneous rate” was elicited by OC activation in fibers if threshold sensitivity approached -10 dB SPL. This “enhancement-in-quiet” appears to arise when an animal-generated noise produces a continuous response (in the absence of purposely applied sound) that is suppressed by OC activity. This finding raises questions as to the range of “true” spontaneous rates in the cat. 6. The results highlight two important distinctions between the effects of OC feedback in quiet versus those in noise. In quiet, the effects are predominately suppressive and are restricted to stimuli at frequencies near a fiber's CF and at intensities within its dynamic range. In continuous background noise, the OC reflex can enhance the responses to transient stimuli. Such effects are seen throughout the fiber's response area.(ABSTRACT TRUNCATED AT 400 WORDS)

Two-tone suppression in the basilar membrane of the cochlea: mechanical basis of auditory-nerve rate suppression

1992 ◽  
Vol 68 (4) ◽  
pp. 1087-1099 ◽  
Author(s):  
M. A. Ruggero ◽  
L. Robles ◽  
N. C. Rich
Keyword(s):  
Auditory Nerve ◽  
Outer Hair Cell ◽  
Basilar Membrane ◽  
Frequency Tuning ◽  
Low Frequency ◽  
Nerve Fibers ◽  
Oval Window ◽  
Outer Hair Cells ◽  
Probe Intensity ◽  
Rate Suppression

1. The vibratory response to two-tone stimuli was measured in the basilar membrane of the chinchilla cochlea by means of the Mossbauer technique or laser velocimetry. Measurements were made at sites with characteristic frequency (CF, the frequency at which an auditory structure is most sensitive) of 7-10 kHz, located approximately 3.5 mm from the oval window. 2. Two-tone suppression (reduction in the response to one tone due to the presence of another) was demonstrated for CF probe tones and suppressor tones with frequencies both higher and lower than CF, at moderately low stimulus levels, including probe-suppressor combinations for which responses to the suppressor were lower than responses to the probe tone alone. 3. For a fixed suppressor tone, suppression magnitude decreased as a function of increasing probe intensity. 4. The magnitude of suppression increased monotonically with suppressor intensity. 5. The rate of growth of suppression magnitude with suppressor intensity was higher for suppressors in the region below CF than for those in the region above CF. 6. For low-frequency suppressor tones, suppression magnitude varied periodically, attaining one or two maxima within each period of the suppressor tone. 7. Suppression was frequency tuned: for either above-CF or below-CF suppressor tones, suppression magnitude reached a maximum for probe frequencies near CF. 8. Cochlear damage or death diminished or abolished suppression. There was a clear positive correlation between magnitude of suppression and basilar-membrane sensitivity for responses to CF tones. 9. Suppression tended to be accompanied by small phase lags in responses to CF probe tones. 10. Because all of the features of two-tone suppression at the basilar membrane match qualitatively (and, generally, also quantitatively) the features of two-tone rate suppression in auditory-nerve fibers, it is concluded that neural two-tone rate suppression originates in mechanical phenomena at the basilar membrane. 11. Because the lability of mechanical suppression parallels the loss of sensitivity and frequency tuning due to outer hair cell dysfunction, the present findings suggest that mechanical two-tone suppression arises from an interaction between the outer hair cells and the basilar membrane.

scholarly journals Fine frequency tuning in monkey auditory cortex and thalamus

2011 ◽  
Vol 106 (2) ◽  
pp. 849-859 ◽  
Author(s):  
Edward L. Bartlett ◽  
Srivatsun Sadagopan ◽  
Xiaoqin Wang
Keyword(s):  
Auditory Cortex ◽  
Auditory Nerve ◽  
Animal Studies ◽  
De Novo ◽  
Frequency Tuning ◽  
Primary Auditory Cortex ◽  
Auditory Pathway ◽  
Nerve Fibers ◽  
Frequency Resolution ◽  
Human Auditory Cortex

The frequency resolution of neurons throughout the ascending auditory pathway is important for understanding how sounds are processed. In many animal studies, the frequency tuning widths are about 1/5th octave wide in auditory nerve fibers and much wider in auditory cortex neurons. Psychophysical studies show that humans are capable of discriminating far finer frequency differences. A recent study suggested that this is perhaps attributable to fine frequency tuning of neurons in human auditory cortex (Bitterman Y, Mukamel R, Malach R, Fried I, Nelken I. Nature 451: 197–201, 2008). We investigated whether such fine frequency tuning was restricted to human auditory cortex by examining the frequency tuning width in the awake common marmoset monkey. We show that 27% of neurons in the primary auditory cortex exhibit frequency tuning that is finer than the typical frequency tuning of the auditory nerve and substantially finer than previously reported cortical data obtained from anesthetized animals. Fine frequency tuning is also present in 76% of neurons of the auditory thalamus in awake marmosets. Frequency tuning was narrower during the sustained response compared to the onset response in auditory cortex neurons but not in thalamic neurons, suggesting that thalamocortical or intracortical dynamics shape time-dependent frequency tuning in cortex. These findings challenge the notion that the fine frequency tuning of auditory cortex is unique to human auditory cortex and that it is a de novo cortical property, suggesting that the broader tuning observed in previous animal studies may arise from the use of anesthesia during physiological recordings or from species differences.

scholarly journals Threshold Tuning Curves of Chinchilla Auditory-Nerve Fibers. I. Dependence on Characteristic Frequency and Relation to the Magnitudes of Cochlear Vibrations

2008 ◽  
Vol 100 (5) ◽  
pp. 2889-2898 ◽  
Author(s):  
Andrei N. Temchin ◽  
Nola C. Rich ◽  
Mario A. Ruggero
Keyword(s):  
Auditory Nerve ◽  
Basilar Membrane ◽  
Frequency Tuning ◽  
Nerve Fibers ◽  
Lower Limbs ◽  
Gradual Transition ◽  
Characteristic Frequencies ◽  
Tuning Curves ◽  
Auditory Nerve Fibers ◽  
Threshold Tuning

Frequency-threshold tuning curves were recorded in thousands of auditory-nerve fibers (ANFs) in chinchilla. Synthetic tuning curves with 21 characteristic frequencies (187 Hz to 19.04 kHz, spaced every 1/3 octave) were constructed by averaging individual tuning curves within 2/3-octave frequency bands. Tuning curves undergo a gradual transition in symmetry at characteristic frequencies (CFs) of 1 kHz and an abrupt change in shape at CFs of 3–4 kHz. For CFs ≤3 kHz, the lower limbs of tuning curves have similar slopes, about −18 dB/octave, but the upper limbs have slopes that become increasingly steep with increasing frequency and CF. For CFs >4 kHz, tuning curves normalized to the CF are nearly identical and consist of three segments. A tip segment, within 30–40 dB of CF threshold, has lower- and upper-limb slopes of −60 and +120 dB/octave, respectively, and is flanked by a low-frequency (“tail”) segment, with shallow slope, and a terminal high-frequency segment with very steep slope (several hundreds of dB/octave). The tuning curves of fibers innervating basal cochlear sites closely resemble basilar-membrane tuning curves computed with low isovelocity criteria. At the apex of the chinchilla cochlea, frequency tuning is substantially sharper for ANFs than for available recordings of organ of Corti vibrations.

scholarly journals Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates

2013 ◽  
Vol 110 (3) ◽  
pp. 577-586 ◽  
Author(s):  
Adam C. Furman ◽  
Sharon G. Kujawa ◽  
M. Charles Liberman
Keyword(s):  
Auditory Nerve ◽  
Dynamic Range ◽  
Frequency Tuning ◽  
Nerve Fibers ◽  
Sensory Cells ◽  
High Threshold ◽  
Distortion Product ◽  
Selective Loss ◽  
Brainstem Response ◽  
Auditory Nerve Fibers

Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds ( Kujawa and Liberman 2009 ), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system.

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