Guinea Pig Auditory Nerve Fibers Research Articles

Salicylate decreases the spontaneous firing rate of guinea pig auditory nerve fibres

Tinnitus has similarities to chronic neuropathic pain where there are changes in the firing rate of different types of afferent neurons. We postulated that one possible cause of tinnitus is a change in the distribution of spontaneous firing rates in at least one type of afferent auditory nerve fibre in anaesthetised guinea pigs. In control animals there was a bimodal distribution of spontaneous rates, but the position of the second mode was different depending upon whether the fibres responded best to high (> 4 kHz) or low (≤4 kHz) frequency tonal stimulation. The simplest and most reliable way of inducing tinnitus in experimental animals is to administer a high dose of sodium salicylate. The distribution of the spontaneous firing rates was different when salicylate (350 mg/kg) was administered, even when the sample was matched for the distribution of characteristic frequencies in the control population. The proportion of medium spontaneous rate fibres (MSR, 1≤ spikes/s ≤20) increased while the proportion of the highest, high spontaneous firing rate fibres (HSR, > 80 spikes/s) decreased following salicylate. The median rate fell from 64.7 spikes/s (control) to 35.4 spikes/s (salicylate); a highly significant change (Kruskal-Wallis test p < 0.001). When the changes were compared with various models of statistical probability, the most accurate model was one where most HSR fibres decreased their firing rate by 32 spikes/s. Thus, we have shown a reduction in the firing rate of HSR fibres that may be related to tinnitus.

Prediction and control of neural responses to pulsatile electrical stimulation

This paper aims to predict and control the probability of firing of a neuron in response to pulsatile electrical stimulation of the type delivered by neural prostheses such as the cochlear implant, bionic eye or in deep brain stimulation. Using the cochlear implant as a model, we developed an efficient computational model that predicts the responses of auditory nerve fibers to electrical stimulation and evaluated the model's accuracy by comparing the model output with pooled responses from a group of guinea pig auditory nerve fibers. It was found that the model accurately predicted the changes in neural firing probability over time to constant and variable amplitude electrical pulse trains, including speech-derived signals, delivered at rates up to 889 pulses s−1. A simplified version of the model that did not incorporate adaptation was used to adaptively predict, within its limitations, the pulsatile electrical stimulus required to cause a desired response from neurons up to 250 pulses s−1. Future stimulation strategies for cochlear implants and other neural prostheses may be enhanced using similar models that account for the way that neural responses are altered by previous stimulation.

Across-Channel Timing Differences as a Potential Code for the Frequency of Pure Tones

When a pure tone or low-numbered harmonic is presented to a listener, the resulting travelling wave in the cochlea slows down at the portion of the basilar membrane (BM) tuned to the input frequency due to the filtering properties of the BM. This slowing is reflected in the phase of the response of neurons across the auditory nerve (AN) array. It has been suggested that the auditory system exploits these across-channel timing differences to encode the pitch of both pure tones and resolved harmonics in complex tones. Here, we report a quantitative analysis of previously published data on the response of guinea pig AN fibres, of a range of characteristic frequencies, to pure tones of different frequencies and levels. We conclude that although the use of across-channel timing cues provides an a priori attractive and plausible means of encoding pitch, many of the most obvious metrics for using that cue produce pitch estimates that are strongly influenced by the overall level and therefore are unlikely to provide a straightforward means for encoding the pitch of pure tones.

A novel stimulus artifact removal technique for high-rate electrical stimulation

Electrical stimulus artifact corrupting electrophysiological recordings often makes the subsequent analysis of the underlying neural response difficult. This is particularly evident when investigating short-latency neural activity in response to high-rate electrical stimulation. We developed and evaluated an off-line technique for the removal of stimulus artifact from electrophysiological recordings. Pulsatile electrical stimulation was presented at rates of up to 5000 pulses/s during extracellular recordings of guinea pig auditory nerve fibers. Stimulus artifact was removed by replacing the sample points at each stimulus artifact event with values interpolated along a straight line, computed from neighbouring sample points. This technique required only that artifact events be identifiable and that the artifact duration remained less than both the inter-stimulus interval and the time course of the action potential. We have demonstrated that this computationally efficient sample-and-interpolate technique removes the stimulus artifact with minimal distortion of the action potential waveform. We suggest that this technique may have potential applications in a range of electrophysiological recording systems.

Auditory nerve response to broadband noise with high-frequency spectral notches

The threshold notch depth for discriminating between a flat-spectrum broadband noise and a similar noise with a rectangular spectral notch centered at 8 kHz varies nonmonotonically with stimulus level (Alves-Pinto and Lopez-Poveda, submitted to J. Acoust. Soc. Am.). A possible explanation for this result is that the notch may be encoded in the rate profile of auditory nerve (AN) fibers with high spontaneous rate (HSR) at low levels and in that of low spontaneous rate (LSR) fibers at high levels. To test this hypothesis, the rate profile of guinea pig AN fibers was measured in response to broadband notched noise for different notch depths and widths and for overall levels ranging from 40 to 100 dB SPL. Preliminary results support the hypothesis that HSR fibers can encode the spectral notch only for levels up to around 70 dB SPL. However, they also suggest that, as in the psychophysics, the negative effect of level is less pronounced the wider the notch. Additional data are required to confirm the role of LSR fibers to encode for the notch at higher levels. [Work supported by Spanish FIS PI020343 and G03/203.]

The diameters of guinea pig auditory nerve fibres: Distribution and correlation with spontaneous rate

In the mammalian auditory nerve physiological recordings revealed that the spontaneous discharge rate of single auditory fibres correlates with the diversity of input-output functions which may be important for intensity discrimination (e.g., Sachs and Abbas, 1974, Liberman, 1978; Winter et al., 1990). In this study we determined if the spontaneous discharge rate of auditory nerve fibres in the guinea pig is correlated with an anatomical feature, namely the diameter of the respective fibres. The diameter of myelinated (Type I) guinea pig auditory nerve fibres was measured after staining with different techniques. Measurements were made on semithin sections using a video image analysis system. The diameters of fibres stained with toluidine blue from the portion of the auditory nerve containing fibres from the basal turn of the cochlea were found to have a normal distribution. Fibres were also labelled with horseradish peroxidase by bulk injection into the spiral ganglion. It was found that the presence of horseradish peroxidase within the fibres reduced the measured diameter in comparison to adjacent unlabelled fibres. A number of fibres were physiologically characterized with respect to spontaneous discharge rate and subsequently intracellularly labelled with horseradish peroxidase. Fibre diameter of a selected sample of intracellularly labelled fibres was measured over a distance of 800 μm within the internal auditory meatus. At the positions nearest to the spiral ganglion fibres possessing low spontaneous rates were found to have smaller diameters than high spontaneous rate fibres. No difference in fibre diameter was found for the positions near the cochlear nucleus.

Diversity of characteristic frequency rate-intensity functions in guinea pig auditory nerve fibres

Rate-intensity functions at characteristic frequency (CF) were recorded from single fibres in the auditory nerve of anaesthetised guinea pigs. Within the same animal, CF rate-intensity functions, although probably forming a continuum, could be conveniently divided into three groups; (1) Saturating; reach maximum discharge rate within 30 dB of threshold, (2) Sloping-saturation; initially rapid growth in discharge rate leading to a slower growth in discharge rate but not saturating and (3) Straight; approximately constant increase in firing rate per decibel increase in sound pressure up to the maximum sound pressures used. Thresholds for individual fibres were plotted relative to compound action potential thresholds at the appropriate frequency. Fibres with straight CF rate-intensity functions had the highest thresholds. Fibres of the saturating CF rate-intensity type had the lowest thresholds, and the sloping-saturation CF rate-intensity type had thresholds intermediate between saturating and straight. There was a close relationship between the type of CF rate-intensity function exhibited by a fibre and its spontaneous discharge rate. Fibres with saturating CF rate-intensity functions generally had high spontaneous discharge rates (greater than 18/s), whereas those with straight CF rate-intensity functions generally had low spontaneous discharge rates (less than 0.5/s). The majority of fibres with sloping-saturation CF rate-intensity functions had spontaneous rates between 0.5/s and 18/s. There was a negative correlation (r = −0.59) between the logarithm of the spontaneous discharge rate and relative threshold at CF with the lowest spontaneous rate fibres having the highest thresholds and vice-versa. This diversity of CF rate-intensity functions has functional implications for both frequency and intensity coding at high sound pressures in the mammalian auditory system.

Responses of gerbil and guinea pig auditory nerve fibers to low-frequency sinusoids.

The characteristics of time-locked auditory nerve fiber responses to 50 Hz acoustic sinusoids were studied in gerbils and guinea pigs. Whereas the time-locked responses of all guinea pig fibers produced single-peaked period histograms, those of the gerbil produced distorted, multiple-peaked response histograms, especially fibers with characteristic frequencies (CFs) between 2 and 10 kHz. Although the shapes of the period histograms vary with stimulus intensity, the phases of the fundamental components are essentially invariant over the range of stimulus intensities used. In contrast to the phase of the cochlear microphonic produced by the 50 Hz stimulus, which was constant along the length of the cochlea in both species, the phase of the neural responses depends on the fiber CF in each of the two species. In guinea pigs, the phase of the neural responses relative to the acoustic stimulus decreases with the fiber CF from a phase lead of 90 degrees for fibers with CFs below 300 Hz to a phase lag of nearly 60 degrees for fibers with CFs greater than 3 kHz. In gerbils, the response phase also decreases with increasing CF below 2 kHz and above 10 kHz but undergoes an abrupt 160 degrees phase increase between those frequencies.

Auditory-nerve correlates of loudness summation with stimulus bandwidth, in normal and pathological cochleae.

The firing of guinea pig auditory nerve fibres was measured in response to bands of noise of many different bandwidths, centre frequencies and intensities. The total amount of activity in the auditory nerve fibre array was calculated as a function of the bandwidth and intensity of the stimulus. As the bandwidth of the stimulus increased, while its net intensity was kept constant, the total firing rate increased steadily. There was no sign of a breakpoint corresponding to the critical bandwidth, seen in psychophysical judgements of loudness with similar stimuli. Moreover, the slope of the relation between total activity and stimulus bandwidth was particularly shallow in fibres with shallow tuning curves. The results suggest that (i) while loudness may in broad terms be related to the total amount of activity in the auditory nerve, this is not true in detail, (ii) the critical bandwidth in loudness summation does not relate to the resolution bandwidth of the cochlea, and (iii) the slope of the psychophysical loudness summation function may be able to give information about the sharpness of neural tuning.

Differences in the CF dependence of response phase of gerbil and guinea pig auditory nerve fibers

Time‐locked responses of auditory nerve fibers to acoustic sinusoids having frequencies between 100 and 400 Hz were studied in gerbils and guinea pigs. With the exception of the responses of gerbil fibers with CFs above 10 kHz, which produce double‐peaked histograms, the responses of most fibers in both species produce single‐peaked histograms when the modulation of spontaneous activity is less than 100%. Within this restricted modulation range, the preferred phase of response is relatively independent of stimulus amplitude. Nonetheless, the variation of the response phase with CF is fundamentally different in the two species. Whereas gerbil fibers show an abrupt 180° phase transition in the CF range between 2 and 4 kHz, the response phase of guinea pig fibers is CF‐independent for stimulus frequencies that are at least 12 octave below fiber CF. The finding of different phase functions in the two species indicates that caution should be exercised in basing models of the neural excitation process in the cochlea solely on data obtained from one mammalian species.

Response differences in gerbil and guinea pig auditory nerve fibers for low frequency sinusoidal acoustic stimuli

Time locked responses of auditory nerve fibers to a 50-Hz sinusoidal acoustic stimulus were studied in both guinea pigs and gerbils. Whereas the time locked responses of all guinea pig fibers resulted in single peaked histograms, those of gerbil auditory nerve fibers resulted in either single, double, or triple peaked histograms. Generally speaking, single peaked histograms are associated with gerbil fibers having CFs below about 2 kHz, double peaked histograms with fibers having CFs between 2 kHz and 8 kHz, and triple peaked histograms with fibers having CFs above 8 kHz. Although the shapes of the histograms vary with stimulus level, the locations of the peaks of maximum response are essentially invariant over the range of stimulus intensities used. In guinea pigs, the relative latency of peak response increases progressively with increasing fiber CF. In gerbils, the same is true only for fibers having CFs below about 2 kHz. Accordingly, there does not appear to be a CF independent preferred time of occurrence of neural response relative to the acoustic stimulus in either species.

Short-term adaptation in single auditory-nerve fibers—an additive or a multiplicative effect?

In response to tone bursts of constant sound intensity, guinea-pig auditory nerve fibers produce a maximum firing rate at the onset, followed by an adaptation to a quasisteady rate within about 150 msec. On the basis of two main experimental findings, we conclude that this adaptation is inherently additive or linear in nature and not the result of a multiplicative or gain change. Basically, a given increment in intensity causes an equal change in firing rate, whether the increment is added before or after adaptation has occurred. In addition, the relative amount of adaptation appearing in the response to a tone of constant intensity, i.e., the ratio of driven onset response to driven steady-state response, is independent of tone-intensity level. When sufficiently high total firing rates are involved, these findings must be modified to include an apparent saturation that occurs at high rates. However, the overall nonlinear stimulus-response relationship may be accounted for by a nonlinearity which precedes the adaptation process and hence does not effect the above relationships.