Responses Of Auditory Nerve Fibers Research Articles

Transcriptional Regulation of Cortical Interneuron Development: Figure 1.

People with cochlear hearing loss have substantial difficulty understanding speech in real-world listening environments (e.g., restaurants), even with amplification from a modern digital hearing aid. Unfortunately, a disconnect remains between human perceptual studies implicating diminished sensitivity to fast acoustic temporal fine structure (TFS) and animal studies showing minimal changes in neural coding of TFS or slower envelope (ENV) structure. Here, we used general system-identification (Wiener kernel) analyses of chinchilla auditory nerve fiber responses to Gaussian noise to reveal pronounced distortions in tonotopic coding of TFS and ENV following permanent, noise-induced hearing loss. In basal fibers with characteristic frequencies (CFs) &gt;1.5 kHz, hearing loss introduced robust nontonotopic coding (i.e., at the wrong cochlear place) of low-frequency TFS, while ENV responses typically remained at CF. As a consequence, the highest dominant frequency of TFS coding in response to Gaussian noise was 2.4 kHz in noise-overexposed fibers compared with 4.5 kHz in control fibers. Coding of ENV also became nontonotopic in more pronounced cases of cochlear damage. In apical fibers, more classical hearing-loss effects were observed, i.e., broadened tuning without a significant shift in best frequency. Because these distortions and dissociations of TFS/ENV disrupt tonotopicity, a fundamental principle of auditory processing necessary for robust signal coding in background noise, these results have important implications for understanding communication difficulties faced by people with hearing loss. Further, hearing aids may benefit from distinct amplification strategies for apical and basal cochlear regions to address fundamentally different coding deficits. <b>SIGNIFICANCE STATEMENT</b> Speech-perception problems associated with noise overexposure are pervasive in today9s society, even with modern digital hearing aids. Unfortunately, the underlying physiological deficits in neural coding remain unclear. Here, we used innovative system-identification analyses of auditory nerve fiber responses to Gaussian noise to uncover pronounced distortions in coding of rapidly varying acoustic temporal fine structure and slower envelope cues following noise trauma. Because these distortions degrade and diminish the tonotopic representation of temporal acoustic features, a fundamental principle of auditory processing, the results represent a critical advancement in our understanding of the physiological bases of communication disorders. The detailed knowledge provided by this work will help guide the design of signal-processing strategies aimed at alleviating everyday communication problems for people with hearing loss.

Changes Across Time in Spike Rate and Spike Amplitude of Auditory Nerve Fibers Stimulated by Electric Pulse Trains

We undertook a systematic evaluation of spike rates and spike amplitudes of auditory nerve fiber (ANF) responses to trains of electric current pulses. Measures were obtained from acutely deafened cats to examine time-related changes free from the effects of hair-cell and synaptic adaptation. Such data relate to adaptation that likely occurs in ANFs of cochlear-implant users. A major goal was to determine and compare rate adaptation observed at different pulse rates (primarily 250, 1000, and 5000 pulse/s) and describe them using decaying exponential models similar to those used in acoustic studies. Rate-vs.-time functions were best described by two-exponent models and produced time constants similar to (although slightly greater than) the "rapid" and "short-term" components described in acoustic studies. There was little dependence of these time constants on onset spike rate, but pulse-rate effects were noted. Spike amplitude changes followed a time course different from that of rate adaptation consistent with a process related to ANF interspike intervals. The fact that two time constants governed rate adaptation in electrically stimulated and deafened fibers suggests that future computational models of adaptation should not only include hair cell and synapse components, but also components determined by fiber membrane characteristics.

Hearing in renal failure

The incidence of sensorineural hearing loss among patients with chronic renal failure (CRF) is considerably higher than in the general population. Bazzi et al. [1] found an incidence of 77% including patients with mild and very mild hearing loss. Ozturan and Lam [2] found a moderate to severe hearing loss in 46% of the tested patients. The general consensus in audiometric findings among patients with CRF claims a high frequency hearing loss [3,4] with a notch at 6 kHz [2]. Presence of hearing loss and estimation of type and degree constitute one of the most common methods used to investigate the effects of renal disease on the auditory system. Degree of hearing loss may give an indication of the extent of damage to auditory function, whereas the type of hearing loss may distinguish between lesions in the outer and middle ear (conductive hearing loss) or the cochlea and the neural pathways (sensorineural hearing loss). In addition to these indicators, the reports to be reviewed in the following sections have also described auditory function in CRF with methods such as otoacoustic emissions (OAEs) (namely transient evoked OAEs, TEOAEs and distorion product OAEs, DPOAEs), and auditory evoked potentials (AEPs). OAEs are low level sounds emitted by the cochlea in the process of receiving the sound vibrations and transforming them to cellular and neural stimulation. Recording of OAEs implies a functioning cochlea and healthy middle ear mechanism. TEOAEs are produced by the action of the hair cells, and they reflect special characteristics of the stimulus. DPOAEs are produced when the ear is stimulated with a combination of pure tones that are close in frequency (the primary tones). DPOAEs reflect non-linear processes of hair cell motion. Both TEOAEs and DPOAEs are generated by the active cochlear mechanisms responsible for enhancing basilar membrane vibration; this is known as the ‘cochlear amplifier’ [5]. AEPs represent neural activity related to auditory stimulation. They show summated neural energy at the various synaptic levels of the auditory pathway; this activity is generated by specific stimuli and extracted from the ongoing EEG activity by specialized technical manipulation. AEPs are recorded from the scalp representing activity in the cochlea and brainstem, thalamus and cortical areas. They are distinguished in early, middle and late evoked potentials, respectively. AEPs recorded from the cochlea include the cochlear microphonic (CM), the summating potential (SP) and the auditory nerve action potential (AP). The CM originates in the outer hair cells and mirrors the incoming signal. The SP also reflects hair cell function. The auditory nerve AP represents the sum of synchronous responses of auditory nerve fibers at the level of the cochlea. The largest component of the AP is the N1, a characteristic wave that constitutes also the first identifiable component of the auditory brainstem response (ABR). The ABR is also an ‘early’ evoked response, as it reflects neural function along the ascending auditory pathway, from the cochlea to the inferior colliculus. The five distinct waves of the normal ABR waveform are mainly generated by successive nuclei in the ascending auditory pathway: waves I and II originate from the distal and proximal portions of the auditory nerve, respectively, wave III originates from the cochlear nucleus, wave IV originates from the superior olivary complex and wave V originates from the lateral lemniscus/inferior colliculus. Each higher level order wave receives contributions from lower levels of the pathway [6]. The AEP reflecting function from auditory cortical areas is the Auditory Late Response (ALR). Major identifiable waves of the ALR are the N1 and P2 waves. ALR measurements reflect higher-level auditory function [7]. In general, latency of AEP waves indicates speed of neural function, whereas amplitude is a variable indicator of response robustness. The cochlea and kidney have similar physiological mechanisms, namely the active transport of fluid Correspondence and offprint requests to: Dr Chryssoula ThodiPetrou Cyprus, Audiology Center, Kallipoleos and 1Damaskinos Str, 1070, P.O. Box 20739, 1663 Nicosia, Cyprus. Email: DrC@cyprusaudiologycenter.com Nephrol Dial Transplant (2006) 21: 3023–3030

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

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.

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.

Spatiotemporal coding based on the responses of individual auditory-nerve fibers

Spatiotemporal coding has been suggested to provide a robust representation of vowel spectra, pitch, and tones in noise. However, much of the quantitative support has come from modeling studies because of the inherent variability in physiological population studies. A spectro-temporal manipulation procedure (STMP) was developed to simulate spatiotemporal patterns from the responses of individual auditory-nerve (AN) fibers to frequency-shifted stimuli with features placed around the fibers’ best frequency. Individual AN fiber responses from anesthetized cats were measured for vowellike stimuli as a function of vowel and background-noise level. Similar to previous population studies, the STMP results show that spatiotemporal coding of vowel spectra (quantified using ALSR) is more robust than average-rate coding as vowel or background-noise level increases. The STMP results also suggest that the response phase transition near low-frequency formants may not be sharp enough to provide as robust encoding as previously suggested. This method of simulating spatiotemporal patterns from individual AN fiber responses may be particularly useful for studying the effects of sensorineural hearing loss because it is particularly difficult to obtain large populations of responses from animals with hearing loss. Preliminary data have been collected from cats with noise-induced hearing loss. [Work supported by NIH/NIDCD R03DC007348.]

Synaptic organization in cochlear inner hair cells deficient for the CaV1.3 (α1D) subunit of L-type Ca2+ channels

Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. Normal development and function of inner hair cells require the expression of α subunit 1.3 forming L-type voltage-gated Ca2+ channel (CaV1.3).Here, we used immunohistochemistry and reverse transcription-polymerase chain reaction to study the synaptic organization and expression of large conductance Ca2+-activated potassium channels in IHCs of mice lacking the CaV1.3 Ca2+ channel (CaV1.3−/−). Despite the near complete block of evoked afferent synaptic transmission, hair cell ribbon synapses were formed and remained preserved for at least 4 weeks after birth. Moreover, these “silent” afferent synapses held major components of the synaptic machinery such as Bassoon, Piccolo, and CSP. Hence, the block of exocytosis might be solely attributed to the lack of Ca2+ influx through CaV1.3 channels. Later on, CaV1.3 deficient IHCs subsequently lost their afferent synapses. This was probably due to a secondary degeneration of the postsynaptic spiral ganglion neurons.In line with a prolonged efferent synaptic transmission onto CaV1.3 deficient IHCs, which normally ceases around onset of hearing, we found juxtaposed immunoreactive spots of efferent presynaptic synaptophysin and postsynaptic (IHCs) small conductance Ca2+-activated potassium channels (SK channels) up to six weeks after birth. Finally, we show a substantial reduction of mRNA for the α subunit of the large conductance Ca2+-activated potassium channel (BK) in the apical cochlea, suggesting a reduced transcription of its gene in CaV1.3 deficient IHCs. CaV1.3 deficient IHCs lacked the apical spot-like immunoreactivity of clustered BK channels, which normally contribute to the temporal precision of hair cell afferent synaptic transmission.In summary, these data indicate that the CaV1.3 channels are crucially involved in regulation of the expression of BK and SK channels. CaV1.3 channels seem not to be essential for ribbon synapse formation, but are required for the maintenance of ribbon synapses and spiral ganglion neurons.

Analysis of models for the synapse between the inner hair cell and the auditory nerve

A general mathematical approach was proposed to study phenomenological models of the inner-hair-cell and auditory-nerve (AN) synapse complex. Two models (Meddis, 1986; Westerman and Smith, 1988) were studied using this unified approach. The responses of both models to a constant-intensity stimulus were described mathematically, and the relationship between model parameters and response characteristics was investigated. The mathematical descriptions of the two models were essentially equivalent despite their structural differences. This analytical approach was used to study the effects of adaptation characteristics on model parameters and of model parameters on adaptation characteristics. The results provided insights into these models and the underlying biophysical processing. This analytical method was also used to study offset adaptation, and it was found that the offset adaptation of both models was limited by the models' structures. A modified version of the synapse model, which has the same onset adaptation but improved offset adaptation, is proposed here. This modified synapse model produces more physiologically realistic offset adaptation and also enhances the modulation gain of model AN fiber responses, consistent with AN physiology.

Wiener Kernels of Chinchilla Auditory-Nerve Fibers: Verification Using Responses to Tones, Clicks, and Noise and Comparison With Basilar-Membrane Vibrations

Responses to tones, clicks, and noise were recorded from chinchilla auditory-nerve fibers (ANFs). The responses to noise were analyzed by computing the zeroth-, first-, and second-order Wiener kernels (h0, h1, and h2). The h1s correctly predicted the frequency tuning and phases of responses to tones of ANFs with low characteristic frequency (CF). The h2s correctly predicted the frequency tuning and phases of responses to tones of all ANFs, regardless of CF. Also regardless of CF, the kernels jointly predicted about 77% of the features of ANF responses to "frozen" samples of noise. Near-CF group delays of kernels and signal-front delays of responses to intense rarefaction clicks exceeded by 1 ms the corresponding basilar-membrane delays at both apical and basal sites of the chinchilla cochlea. This result, confirming that synaptic and neural processes amount to 1 ms regardless of CF, permitted drawing a map of basilar-membrane delay as a function of position for the entire length of the chinchilla cochlea, a first for amniotic species.

Encoding of vowel-like sounds in the auditory nerve: Model predictions of discrimination performance

The sensitivity of listeners to changes in the center frequency of vowel-like harmonic complexes as a function of the center frequency of the complex cannot be explained by changes in the level of the stimulus [Lyzenga and Horst, J. Acoust. Soc. Am. 98, 1943-1955 (1995)]. Rather, a complex pattern of sensitivity is seen; for a spectrum with a triangular envelope, the greatest sensitivity occurs when the center frequency falls between harmonics, whereas for a spectrum with a trapezoidal envelope, greatest sensitivity occurs when the center frequency is aligned with a harmonic. In this study, the thresholds of a population model of auditory-nerve (AN) fibers were quantitatively compared to these trends in psychophysical thresholds. Single-fiber and population model responses were evaluated in terms of both average discharge rate and the combination of rate and timing information. Results indicate that phase-locked responses of AN fibers encode phase transitions associated with minima in these amplitude-modulated stimuli. The temporal response properties of a single AN fiber, tuned to a frequency slightly above the center frequency of the harmonic complex, were able to explain the trends in thresholds for both triangular- and trapezoidal-shaped spectra.

The Relationship between Musical Pitch and Temporal Responses of the Auditory Nerve Fibers

To investigate how the high pitched notes in a musical score are played on the piccolo, nine flutists produced tones of a C major scale, from C6 to C8, using their own piccolo. The fundamental frequency of each tone was measured. The results showed that all tones were produced higher in frequency than the theoretical values and that this tendency was striking in the higher frequency range. This phenomenon is discussed in terms of temporal responses of auditory nerve fibers.

Erratum: “A phenomenological model for the responses of auditory-nerve fibers: II. Nonlinear tuning with a frequency glide” [J. Acoust. Soc. Am. 114, 2007–2020 (2003)

The schematic diagram and text erroneously omitted a component of the auditory-nerve model. A first-order low-pass filter with a cutoff frequency of 500 Hz was included in the feedback path within the model’s control-path, as shown here ~LP2, Fig. 1!; a scalar K with a value of 10 followed the low-pass filter in the feedback path. This low-pass filter was included in some but not all of the simulations shown in the original paper, as clarified below. The inclusion of LP2 did not significantly affect responses to pure tone stimuli ~Tan and Carney, 2003, Figs. 7–9,11,12! or to broadband noise ~Tan and Carney, 2003, Figs. 4,10!. The low-pass filter ~LP2! mainly affected responses to two-tone stimuli, and in particular was responsible for introducing the differences in growth of suppression for tones below or above CF. Figure 13 in Tan and Carney ~2003! did not include LP2; Fig. 2 here illustrates the effect of its inclusion. Figure 14 in Tan and Carney ~2003! did include LP2; the effects of its inclusion are illustrated here in Fig. 3.

Temporal resolution and temporal integration of short pulses at the auditory periphery of echolocating animals

To explain the temporal integration and temporal resolution abilities revealed in echolocating animals by behavioral and electrophysiological experiments, the peripheral coding of sounds in the high-frequency auditory system of these animals is modeled. The stimuli are paired pulses similar to the echolocating signals of the animals. Their duration is comparable with or smaller than the time constants of the following processes: formation of the firing rate of the basilar membrane, formation of the receptor potentials of internal hair cells, and recovery of the excitability of spiral ganglion neurons. The models of auditory nerve fibers differ in spontaneous firing rate, response thresholds, and abilities to reproduce small variations of the stimulus level. The formation of the response to the second pulse of a pair of pulses in the multitude of synchronously excited high-frequency auditory nerve fibers may occur in only two ways. The first way defined as the stochastic mechanism implies the formation of the response to the second pulse as a result of the responses of the fibers that did not respond to the first pulse. This mechanism is based on the stochastic nature of the responses of auditory nerve fibers associated with the spontaneous firing rate. The second way, defined as the repeatition mechanism, implies the appearance of repeated responses in fibers that already responded to the first pulse but suffered a decrease in their response threshold after the first spike generation. This mechanism is based on the deterministic nature of the responses of fibers associated with refractoriness. The temporal resolution of pairs of short pulses, which, according to the data of behavioral experiments, is about 0.1–0.2 ms, is explained by the formation of the response to the second pulse through the stochastic mechanism. A complete recovery of the response to the second pulse, which, according to the data of electrophysiological studies of short-latency evoked brainstem potentials in dolphins, occurs within 5 ms, is explained by the formation of the response to the second pulse through the repetition mechanism. The time constant of temporal integration, which, according to the behavioral experiments at threshold levels of pulses, is about 0.2–0.3 ms, is explained by the integrating properties of internal hair cells, etc. It is shown that, at the high-frequency auditory periphery, the temporal integration imposes no limitations on the temporal resolution, because both integration and resolution are different characteristics of the same multiple response of synchronously excited fibers.

Neural mechanisms for spectral segregation

Humans exhibit a remarkable ability to segregate sounds produced by multiple sources that overlap in frequency and in time. It is likely that other species that use hearing also have this ability. To investigate the neural mechanisms that contribute to spectral segregation, responses of auditory nerve fibers (ANFs) and inferior colliculus (IC) neurons to harmonic complex tones and to the same tones with a mistuned component were measured. Mistuning leads to the perception of a new sound source and also produces dramatic qualitative changes in the temporal discharge patterns of IC neurons. In contrast, the same stimulus manipulation produces only modest quantitative changes in the responses of ANFs. These results indicate that the processing of complex tones undergoes a major transformation in the lower brainstem that is likely to contribute to perceptual segregation based on harmonicity. A computational model has been developed to investigate integrative mechanisms that may underlie this transformation. The model reproduces the distinctive discharge patterns of IC neurons, and suggests that these patterns arise as a result of narrow-band envelope extraction, followed by broadband excitatory–inhibitory interactions. Specific predictions of the model have been confirmed in subsequent electrophysiological experiments, providing further support for this interpretation. [Work supported by NIDCD.]

Predicting auditory tone-in-noise detection performance: the effects of neural variability.

Collecting and analyzing psychophysical data is a fundamental mechanism for the study of auditory processing. However, because this approach relies on human listening experiments, it can be costly in terms of time and money spent gathering the data. The development of a theoretical, model-based procedure capable of accurately predicting psychophysical behavior could alleviate these issues by enabling researchers to rapidly evaluate hypotheses prior to conducting experiments. This approach may also provide additional insight into auditory processing by establishing a link between psychophysical behavior and physiology. Signal detection theory has previously been combined with an auditory model to generate theoretical predictions of psychophysical behavior. Commonly, the ideal processor outperforms human subjects. In order for this model-based technique to enhance the study of auditory processing, discrepancies must be eliminated or explained. In this paper, we investigate the possibility that neural variability, which results from the randomness inherent in auditory nerve fiber responses, may explain some of the previously observed discrepancies. In addition, we study the impact of combining information across nerve fibers and investigate several models of multiple-fiber signal processing. Our findings suggest that neural variability can account for much, but not all, of the discrepancy between theoretical and experimental data.

CaV1.3 Channels Are Essential for Development and Presynaptic Activity of Cochlear Inner Hair Cells

Cochlear inner hair cells (IHCs) release neurotransmitter onto afferent auditory nerve fibers in response to sound stimulation. During early development, afferent synaptic transmission is triggered by spontaneous Ca2+ spikes of IHCs, which are under efferent cholinergic control. Around the onset of hearing, large-conductance Ca2+-activated K+ channels are acquired, and Ca2+ spikes as well as the cholinergic innervation are lost. Here, we performed patch-clamp measurements in IHCs of mice lacking the CaV1.3 channel (CaV1.3-/-) to investigate the role of this prevailing voltage-gated Ca2+ channel in IHC development and synaptic function. The small Ca2+ current remaining in IHCs from 3-week-old CaV1.3-/- mice was mainly mediated by L-type Ca2+ channels, because it was sensitive to dihydropyridines but resistant to inhibitors of non-L-type Ca2+ channels such as omega-conotoxins GVIA and MVIIC and SNX-482. Depolarization induced only marginal exocytosis in CaV1.3-/- IHC, which was solely mediated by L-type Ca2+ channels, whereas robust exocytic responses were elicited by photolysis of caged Ca2+. Secretion triggered by short depolarizations was reduced proportionally to the Ca2+ current, suggesting that the coupling of the remaining channels to exocytosis was unchanged. CaV1.3-/- IHCs lacked the Ca2+ action potentials and displayed a complex developmental failure. Most strikingly, we observed a continued presence of efferent cholinergic synaptic transmission and a lack of functional large-conductance Ca2+-activated K+ channels up to 4 weeks after birth. We conclude that CaV1.3 channels are essential for normal hair cell development and synaptic transmission.

Desynchronization of electrically evoked auditory-nerve activity by high-frequency pulse trains of long duration.

Rubinstein et al. [Hear. Res. 127, 108-118 (1999)] suggested that the neural representation of the waveforms of electric stimuli might be improved by introducing an ongoing, high-rate, desynchronizing pulse train (DPT). A DPT may desynchronize neural responses to electric stimulation in a manner similar to spontaneous activity in a healthy ear. To test this hypothesis, responses of auditory-nerve fibers (ANFs) to 10-min-long electric pulse trains (5 kpps) were recorded from acutely deafened, anesthetized cats. Stimuli were delivered via an intracochlear electrode, and their amplitude was chosen to elicit a response in most ANFs. Responses to pulse trains showed pronounced adaptation during the first 1-2 min, followed by either a sustained response or cessation of spike discharges for the remainder of the stimulus. The adapted discharge rates showed a broad distribution across the ANF population like spontaneous activity. However, a higher proportion of fibers (46%) responded to the DPT at rates below 5 spikes/s than for spontaneous activity, and 12% of the fibers responded at higher rates than any spontaneously active fiber. Interspike interval histograms of sustained responses for some fibers had Poisson-like (exponential) shapes, resembling spontaneous activity, while others exhibited preferred intervals and, occasionally, bursting. Simultaneous recordings from pairs of fibers revealed no evidence of correlated activity, suggesting that the DPT does desynchronize the auditory nerve activity. Overall, these results suggest that responses to an ongoing DPT resemble spontaneous activity in a normal ear for a substantial fraction of the ANFs.

A phenomenological model for the responses of auditory-nerve fibers. II. Nonlinear tuning with a frequency glide

A computational model was developed to simulate the responses of auditory-nerve (AN) fibers in cat. The model's signal path consisted of a time-varying bandpass filter; the bandwidth and gain of the signal path were controlled by a nonlinear feed-forward control path. This model produced realistic response features to several stimuli, including pure tones, two-tone combinations, wideband noise, and clicks. Instantaneous frequency glides in the reverse-correlation (revcor) function of the model's response to broadband noise were achieved by carefully restricting the locations of the poles and zeros of the bandpass filter. The pole locations were continuously varied as a function of time by the control signal to change the gain and bandwidth of the signal path, but the instantaneous frequency profile in the revcor function was independent of sound pressure level, consistent with physiological data. In addition, this model has other important properties, such as nonlinear compression, two-tone suppression, and reasonable Q10 values for tuning curves. The incorporation of both the level-independent frequency glide and the level-dependent compressive nonlinearity into a phenomenological model for the AN was the primary focus of this work. The ability of this model to process arbitrary sound inputs makes it a useful tool for studying peripheral auditory processing.

Discharge properties of identified cochlear nucleus neurons and auditory nerve fibers in response to repetitive electrical stimulation of the auditory nerve.

Using the in vitro isolated whole brain preparation of the guinea pig maintained at 29 degrees C, we intracellularly recorded and stained cochlear nucleus (CN) neurons and auditory nerve (AN) fibers. Discharge properties of CN cells and AN axons were tested in response to 50-ms trains of electrical pulses delivered to the AN at rates ranging from 100 to 1000 pulses per second (pps). At low stimulation rates (200-300 pps), the discharges of AN fibers and a large proportion of principal cells (bushy, octopus, stellate) in the ventral cochlear nucleus (VCN) followed with high probability each pulse in the train, resulting in synchronization of discharges within large populations of AN fibers and CN cells. In contrast, at high stimulation rates (500 pps and higher), AN fibers and many VCN cells exhibited "primary-like", "onset" and some other discharge patterns resembling those produced by natural sound stimuli. Unlike cells in the VCN, principal cells (pyramidal, giant) of the dorsal CN did not follow the stimulating pulses even at low rates. Instead, they often showed "pauser" and "build-up" patterns of activity, characteristic for these cells in conditions of normal hearing. We hypothesize that, at low stimulation rates, the response behavior of AN fibers and VCN cells is different from the patterns of neuronal activity related to normal auditory processing, whereas high stimulation rates produce more physiologically meaningful discharge patterns. The observed differences in discharge properties of AN fibers and CN cells at different stimulation rates can contribute to significant advantages of high- versus low-rate electrical stimulation of the AN used for coding sounds in modern cochlear implants.

Auditory nerve fibre responses to salicylate revisited

Ototoxicity of salicylate is accompanied by a temporary hearing loss and tinnitus and has therefore been used to study tinnitus in animal models. Salicylate induced elevated central auditory activity has been interpreted as a correlate of tinnitus. Whether this elevated activity in the central auditory system is due to an increased activity in the auditory nerve is still under discussion. To explore this issue, we recorded the activity of single auditory nerve fibres in anaesthetised gerbils following systemic injection of salicylic acid. Firstly, compound action potential (CAP) thresholds were determined at 5–0 min intervals. Fifteen to 30 min after 200 mg/kg salicylic acid, threshold loss developed in the high frequency range. At 2 h CAP threshold loss reached a plateau amounting to 15–20 dB above 16 kHz, 0–5 dB below 2 kHz. An almost immediate start of threshold loss was observed after 400 mg/kg salicylic acid. A plateau of threshold loss was reached after 1.5 h with values of 25 dB in the high, 5–10 dB in the low frequency range. Secondly, responses of single auditory nerve fibres were studied after administration of 200 mg/kg salicylic acid. Frequency tuning curves and rate intensity (RI) functions at characteristic frequency (CF) were measured. Two hours and more after application, single fibre thresholds were elevated by about 20 dB at all CFs. Sharpness of tuning was reduced. Mean spontaneous rate was significantly reduced at CFs below 5 kHz (mean: 44 vs 28 AP/s). At CFs above 5 kHz mean spontaneous rate remained unchanged. In RI functions no change in maximum discharge rate was observed. The altered response properties can be interpreted by the known effects of salicylate on the prestin mediated active process of the outer hair cells. The elevated activity in the central auditory system after salicylate intoxication thus cannot be caused by cochlear nerve hyperactivity.