Eighth nerve fiber firing features in normal-hearing rabbits

Neural activity of single eighth nerve fibers was recorded with glass microelectrodes in anesthetized normal-hearing rabbits. The units had a spontaneous rate ranging from 0 to approximately 120 spikes/s. In a large number of fibers this rate was below 2 spikes/s. The frequency tuning curves (FTCs) had a tip and a tail region for fibers with a high or medium characteristic frequency (CF). For low-frequency units the FTC was more symmetrically U-shaped. The tip threshold reached the behavioral threshold and units with thresholds of up to more than 60 dB above the mean behavioral threshold were found. There was a weak negative correlation between spontaneous rate and tip threshold. Frequency selectivity, Q10, was about 2 for units with CF below 2 kHz and about 5 for those with CF above 4 kHz. The peristimulus time (PST) histogram showed an initial peak, a plateau, and poststimulus inhibition. For the majority of fibers the dynamic range was 20-30 dB. Some fibers did not reach saturation within the stimulus intensity available. The tip-to-tail distance was 50 dB for high-frequency units at one octave below CF, a matter of potential interest for further studies of animals with inner ear lesions.     

Acoustic trauma of sportsman hunter due to gun firing

A historical review of acoustic trauma is presented with documented proof of resulting hearing loss and established damage risk criteria for both steady state and impulse noise. A detailed evaluation of impulse noise produced by the weapons and ammunition most frequently used by the sportsman hunter revealed that only a few of the rim firing tests fell short of the damage risk criteria for impulse noise. The muzzle energy exerts the greatest effect on the peak sound pressure level. It is demonstrated that modification of the barrel of the firearm lowered the acoustical energy as much as 97.5 percent. Since most sportsmen hunters decline the use of ear defenders to protect their ears, this method is proposed as an alternative for the conservation of their hearing.     

Acoustic over-exposure triggers burst firing in dorsal cochlear nucleus fusiform cells

Acoustic over-exposure (AOE) triggers deafness in animals and humans and provokes auditory nerve degeneration. Weeks after exposure there is an increase in the cellular excitability within the dorsal cochlear nucleus (DCN) and this is considered as a possible neural correlate of tinnitus. The origin of this DCN hyperactivity phenomenon is still unknown but it is associated with neurons lying within the fusiform cell layer. Here we investigated changes of excitability within identified fusiform cells following AOE. Wistar rats were exposed to a loud (110 dB SPL) single tone (14.8 kHz) for 4 h. Auditory brainstem response recordings performed 3–4 days after AOE showed that the hearing thresholds were significantly elevated by about 20–30 dB SPL for frequencies above 15 kHz. Control fusiform cells fired with a regular firing pattern as assessed by the coefficient of variation of the inter-spike interval distribution of 0.19 ± 0.11 (n = 5). Three to four days after AOE, 40% of fusiform cells exhibited irregular bursting discharge patterns (coefficient of variation of the inter-spike interval distribution of 1.8 ± 0.6, n = 5; p < 0.05). Additionally the maximal firing following step current injections was reduced in these cells (from 83 ± 11 Hz, n = 5 in unexposed condition to 43 ± 6 Hz, n = 5 after AOE) and this was accompanied by an increased firing gain (from 0.09 ± 0.01 Hz/pA, n = 5 in unexposed condition to 0.56 ± 0.25 Hz/pA, n = 5 after AOE). Current and voltage clamp recordings suggest that the presence of bursts in fusiform cells is related to a down regulation of high voltage activated potassium currents.In conclusion we showed that AOE triggers deafness at early stages and this is correlated with profound changes in the firing pattern and frequency of the DCN major output fusiform cells. The changes here described could represent the initial network imbalance prior to the emergence of tinnitus.     

Spectral time-course analysis of firing patterns in the dorsal cochlear nucleus

Many previous studies of central auditory neurons have involved independent analyses of spectral and temporal response properties. The spectral response analysis is useful for defining the frequency and intensity regions over which a neuron is excited or inhibited. However, the conventional spectral response analysis only defines this distribution for the synaptic polarity (excitation or inhibition) which dominates the duration of the response. PST histograms of dorsal cochlear nucleus neurons however, often exhibit both excitatory and inhibitory (i.e. pause) components. The distribution of these transient pause intervals may in turn be highly dependent on stimulus parameters suggesting that the spectral area of excitation and inhibition, when considered in terms of short time frames, may be time-dependent. We performed a temporal analysis of the spectral response areas of neurons in the rat dorsal cochlear nucleus and present here an example based on a neuron showing distinct pauser and buildup responses in its PST histograms. The resulting analysis yielded a time course of the spectral response area which indicates that the transient periods of inhibition may have the effect of narrowing the bandwidth of excitation during the early portion of stimulation. Possible implications of this time course are discussed in relation to the narrower tuning that cochlear nucleus neurons often display in response to frequency sweeps than to pure tones.     

Stimulus induced and spontaneous rhythmic firing of single units in cat primary auditory cortex.

Recordings were made under ketamine anesthesia from 385 neurons in primary auditory cortex in adult cat and from 265 neurons in 10-55 day old kittens. The temporal Modulation Transfer Function for the response to repetitive click stimuli peaked at 8 Hz. After a click a suppression period of 130- 155 ms in duration, depending on click-rate, was observed. This suppression period limited the response to high click rates and thereby determined the 'resonance' in the click response. The suppression duration in kittens decreased in exponential fashion toward the adult value with a time constant of about 1 month. After the one second duration click-trains an oscillatory rebound with a mean period of 113 ms was observed in about 60% of the recordings in the adult cat. Spontaneous activity showed in about 30% of the neurons an oscillatory autocorrelogram with an average period of 126 ms in the adult cats and 170 ms in kittens.     

The firing properties of second-order vestibular neurons in correlation with the far-field recorded vestibular-evoked response

Action potentials of the second-order vestibular neurons of ten cats were recorded, both in rest and responding to sinusoidal and intense impulse acceleration stimuli. The data were compared with the far-field recorded vestibular-evoked response induced by the same impulse stimuli. It was found that the irregular (kinetic) neurons, which had a phase lead relative to head velocity, were capable of responding to these impulses with a latency as short as 3.5 msec after the start of head acceleration. It is assumed, therefore, that these neurons are the generators of the second wave of the vestibular-evoked response, having a similar latency. A high correlation was found between the latency of the first peak in the poststimulus time histogram in response to acceleration impulses and the phase of the response to sinusoidal rotations. The regular (tonic) vestibular neurons did not respond to acceleration impulses and probably did not contribute to the vestibular-evoked response.     

Spontaneous firing activity of cortical neurons in adult cats with reorganized tonotopic map following pure-tone trauma

We hypothesized that moderate sensorineural hearing loss resulting from acoustic trauma would cause (i) a change in the cortical tonotopic map, (ii) an increase in spontaneous activity in the reorganized region and (iii) increased inter-neuronal synchrony within the reorganized part of the cortex. Five kittens were exposed to a 126 dB sound pressure limit tone of 6 kHz for 1 h at both 5 and 6 weeks of age. Recordings were performed 7-16 weeks after the exposure. Auditory brainstem response thresholds for frequencies above 12 kHz were increased by 30 dB on average relative to those in normal cats. Tonotopic maps in the primary auditory cortex were reorganized in such a way that the area normally tuned to frequencies of 10-40 kHz was now entirely tuned to 10 kHz. Spontaneous firing rates were significantly higher in reorganized areas than in normal areas. In order to test for changes in inter-neuronal synchrony, cross-correlation analysis was done on 225 single-unit pairs recorded in the traumatized cats. For the single- and dual-electrode pairs there was no significant difference in peak cross-correlation coefficients for the firings of simultaneously recorded cells between normal and reorganized areas. However, the percentage of correlations that differed significantly from zero was higher in the reorganized area than in the normal area. This suggests a potential correlation between cortical reorganization, increased spontaneous firing rate and inter-neuronal synchrony that might be related to tinnitus found in high-frequency hearing loss induced by acoustic trauma.     

Recovery from prior stimulation. I: Relationship to spontaneous firing rates of primary auditory neurons.

Recovery of neural thresholds following a forward masker was measured for auditory neurons in anesthetized chinchillas. We find that recovery of forward-masked thresholds is slower for low spontaneous-rate neurons compared to high spontaneous-rate neurons. In addition, we studied the dependence of the shape of PST histograms on the time between repetitions of a tone-burst. We find that for low spontaneous-rate neurons, peak onset responses increase in magnitude over a longer range of interstimulus intervals compared to high spontaneous-rate neurons. Both results are consistent with the conclusion that low spontaneous-rate neurons take longer to recover from prior stimulation compared to high spontaneous-rate neurons. We suggest applications of this finding in psychophysical experiments to investigate the role of low spontaneous-rate neurons in intensity coding.     

Effect of a glutamate blocker, ipenoxazone hydrochloride on the hypoxia-induced firing in the medial vestibular nucleus

To elucidate the effectiveness of the drug in the treatment of vertebrobasilar insufficiency (VBI), we performed an electrophysiological study to examine the effects of ipenoxazone hydrochloride, a glutamate blocker, on hypoxia-induced firing in the medial vestibular nucleus (MVN) neuron, using alpha-chloralose-anesthetized cats. The single neuronal activity of the MVN was recorded extracellularly with a glass-insulated silver wire microelectrode attached along a seven-barrel micropipette. The firing rate of MVN neurons showed a transient increase [hypoxic depolarization (HD)] during 5% O(2) inhalation, followed by a gradual decrease and disappearance. HD and the time to disappearance of firing induced by hypoxia were inhibited by iontophoretic application of ipenoxazone hydrochloride. These results suggest that ipenoxazone hydrochloride protects against hypoxic neuronal dysfunction, and may be an effective drug for vertigo caused by VBI.     

Changes in spontaneous firing rate and neural synchrony in cat primary auditory cortex after localized tone-induced hearing loss

Increase in spontaneous neural activity after noise-induced hearing loss has frequently been associated with the phenomenon of tinnitus. Eighteen juvenile and adult cats were exposed for 2 h to a 6 kHz tone with an intensity of 115 dB SPL at the cat’s head. Seven non-exposed littermates and seven other normal hearing cats were used as age-matched controls. The trauma cats showed localized hearing losses, as assessed by ABR, ranging from less than 20 to 60 dB. The frequency representation in primary auditory cortex was mapped using an eight-electrode array. Single-unit spontaneous activity was recorded for 15 min. Peak cross-correlation coefficients (R) for unit cluster activity recorded on separate electrodes were calculated. We found elevated spontaneous firing rates in regions with reorganization of the tonotopic map compared to the neurons in the non-reorganized cortical regions in the same animals. A second finding was that in these regions the peak cross-correlation coefficients were also increased relative to the non-reorganized parts. A third finding was that exposed animals showed higher spontaneous activity compared to controls regardless of the presence of cortical reorganization. This may be a correlate of tinnitus in the presence of only minor hearing losses.     

Relationship between tone burst discharge pattern and spontaneous firing rate of auditory nerve fibres in the guinea pig.

A detailed investigation was carried out of the response of single auditory nerve fibres in the guinea pig to tone bursts. Comparisons were made between the shapes of peri-stimulus-time histograms (PSTHs) of low and high characteristic frequency (CF) fibres grouped according to their spontaneous firing rates (SR). Both low and high CF fibres of high spontaneous rate (greater than 18 spikes/s) exhibited marked rapid adaptation in their PSTH's which became most pronounced at high stimulus intensities. The ratio of onset-to-adapted firing estimated from PSTH data in these fibres increased monotonically as a function of adapted firing rate. The behaviour of fibres with the lowest spontaneous rates (less than 0.5 spikes/s) was markedly different, particularly in fibres from low CF regions. In general, these low-SR fibres showed slower adaptation than high-SR fibres, and a less pronounced onset peak. This was most striking in low CF fibres. Furthermore, the ratio of onset-to-adapted firing rate tended to decrease with increasing stimulus intensity in both low and high CF fibres with low spontaneous firing rates. Low-SR fibres also showed the highest maximum discharge rates to tone burst stimuli. Fibres with medium spontaneous rates between 0.5 and 18 spikes/s displayed intermediate characteristics in their PSTH's. Recent data in the chinchilla (Relkin and Doucet, 1991), suggest that these differences may arise in part from differences in inter-stimulus recovery processes in the different spontaneous rate groups.     

Combined application of brain-derived neurotrophic factor and neurotrophin-3 and its impact on spiral ganglion neuron firing properties and hyperpolarization-activated currents

Neurotrophins provide an effective tool for the rescue and regeneration of spiral ganglion neurons (SGNs) following sensorineural hearing loss. However, these nerve growth factors are also potent modulators of ion channel activity and expression, and in the peripheral auditory system brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) have previously been shown to alter the firing properties of auditory neurons and differentially regulate the expression of some potassium channels in?vitro. In this study we examined the activity of the hyperpolarization-mediated mixed-cation current (I(h)) in early post-natal cultured rat SGNs following exposure to combined BDNF and NT3. Whole-cell patch-clamp recordings made after 1 or 2 days in?vitro revealed no change in the firing adaptation of neurons in the presence of BDNF and NT3. Resting membrane potentials were also maintained, but spike latency and firing threshold was subject to regulation by both neurotrophins and time in?vitro. Current clamp recordings revealed an activity profile consistent with activation of the hyperpolarization-activated current. Rapid membrane hyperpolarization was followed by a voltage- and time-dependent depolarizing voltage sag. In voltage clamp, membrane hyperpolarization evoked a slowly-activating inward current that was reversibly blocked with cesium and inhibited by ZD7288. The amplitude and current density of I(h) was significantly larger in BDNF and NT3 supplemented cultures, but this did not translate to a significant alteration in voltage sag magnitude. Neurotrophins provided at 50?ng/ml produced a hyperpolarizing shift in the voltage-dependence and slower time course of I(h) activation compared to SGNs in control groups or cultured with 10?ng/ml BDNF and NT3. Our results indicate that combined BDNF and NT3 increase the activity of hyperpolarization-activated currents and that the voltage-dependence and activation kinetics of I(h) in SGNs are sensitive to changes in neurotrophin concentration. In addition, BDNF and NT3 applied together induce a decrease in firing threshold, but does not generate a shift in firing adaptation.