Spectrum of neural electrical activity in guinea pig cochlea: effects of anaesthesia regimen, body temperature and ambient noise

Spectral analysis of electric noise recorded from the round window of the cochlea is thought to represent the summed spontaneous activity of the auditory nerve. It has been postulated that it could provide a possible tinnitus index. Because experimental conditions could change this neural activity, the effect of anaesthesia regimen, body temperature and ambient noise on the spectrum of spontaneous neural noise (SNN) were investigated in guinea pig cochlea. SNN was studied in awake guinea pigs and after anaesthesia with pentobarbital (P), xylazine/ketamine (XK) or xylazine/tiletamine-zolazepam (XTZ). Body temperature varied gradually from 33 to 41 degrees C under XK regimen. In awake animals, broadband noise was generated with intensity varying from 0 to 50 dB. The SNN consisted in a broad peak at approximately 900 Hz. With ambient broadband noise, it increased exponentially with the sound level with no shift in frequency. Soon after anaesthetic induction, the lowest frequencies were constantly decreased, and gradually the 900 Hz peak either increased moderately (P) or dropped steeply (XTZ) or remained unchanged (XK). Peak frequency increased linearly with body temperature whereas the amplitude reached a maximum at around 39.5 degrees C. In conclusion, these data indicate that experimental conditions such as anaesthesia regimen, body temperature and ambient noise modify the spontaneous neural outflow of the cochlea and must be taken into account when studying SNN.     

The origin of the 900 Hz spectral peak in spontaneous and sound-evoked round-window electrical activity

We have monitored the spectrum of the (spontaneous) neural noise at the round window (RW) and on the surface of the antero-ventral cochlear nucleus (CN) and the dorsal CN (DCN) of anaesthetised guinea pigs. We have also obtained the average gross extracellular waveform evoked by 20 kHz tone-bursts (0.25 ms and 25 ms) at each of these recording sites, and calculated the spectrum of the average waveforms (SAW). With these tone-bursts, only a small population of neurones in the extreme basal turn of the cochlea near the RW electrode responds, presumably with only a single action potential for each 0.25 ms tone-burst. The RW waveforms recorded between 20 dB and 60 dB SPL were very similar, and are therefore presumably a simple estimate of the shape of the contribution of the firing of a single neurone to the gross RW signal (the unitary potential or UP). In normal animals, the SNN and the SAW were remarkably similar, with peaks at 900 Hz and at 2400 Hz, suggesting that they are not due to neural synchronisation (as suggested previously by others), but are due to an oscillatory waveform produced by each single fibre action potential. Abolition of all spike activity by RW tetrodotoxin left a waveform with only a summating potential and a dendritic potential, and no 900 Hz peak in the SAW or SNN, indicating that the spectral peak is due to neural spiking only. Abolition of the CN contribution to the RW waveforms by CN application of lignocaine or sectioning of the cochlear nerve at the internal meatus (by focal aspiration of the DCN and underlying cochlear nerve) showed that the 900 Hz peak was not simply due to the addition of a delayed and inverted CN contribution: mathematical modelling shows that this would produce a broad spectral peak at about 1200 Hz. Moreover, the 900 Hz spectral peak remains after complete abolition of the CN contribution, although reduced in amplitude. This residual 900 Hz peak can be traced to an oscillation in the gross waveform due to the presence of two peaks (P(1)* and N(2)*) which follow the intact N(1) peak. The P(1)* and N(2)* peaks were present at the RW, but not at the cochlear nerve as it exits the internal meatus, suggesting that they were not due to double-spiking of some of the neurones, but were probably due to a sub-threshold electrical resonance in the peripheral dendrites. We have successfully modelled the production of the SNN and the compound action potential and SAW in response to 0.25 ms and 25 ms tone-bursts at 20 kHz by including only a damped 900 Hz resonance in the UP, without refractory effects, preferred intervals or synchronisation in the timing of neural spike generation. Such resonances in other neurones are known to be due to the activation kinetics of the voltage-controlled sodium (Na(+)) channels of these neurones. The presence of such sub-threshold oscillations probably indicates that the peripheral dendrites are devoid of stabilising potassium (K(+)) channels. We also discuss the role of this membrane resonance in generating burst-firing of the cochlear nerve (as with salicylate) and the role of such burst-firing in generating tinnitus.     

Sealing of the round window reversibly affects auditory brainstem response latencies

The round window (RW) niche was sealed in 12 adult female albino Sprague-Dawley rats. Electrophysiological auditory function was measured with a computerized auditory brainstem response (ABR) recording technique, using 1- and 6 kHz stimuli. ABR measurements were performed prior to closure of the niche, immediately after the sealing, and 4 h, 24 h and 7 days later. After sealing, the latencies elicited by a 6 kHz stimulus increased, but returned to normal between 24 h and 7 days after closure. Stimulation with 1 kHz did not influence the latencies in such a clear-cut manner as when using 6 kHz. It is conceivable that sealing of the RW deprives a minor fraction of oxygen supplied to the basal part of the cochlea through the RW membrane, a procedure which by us is monitored as transient electrophysiological changes.     

人工耳蜗植入术中圆窗耳蜗电图评价耳蜗残余听功能

目的应用术中圆窗耳蜗电图评估极重度感音神经性聋患者耳蜗残余听功能。方法20例患者全麻下人工耳蜗植入手术过程中,行术中圆窗耳蜗电图测试,测出的复合动作电位（CAP）阈值与术前纯音测听或其他听力测试之阈值进行比较。结果20例患者术中圆窗耳蜗电图测试测出的复合动作电位（CAP）阈值与术前1、2、4kHz听力测试阈值分别有较好的相关系数（0．20429,0．04076,0．38163）。结论术中圆窗耳蜗电图可以较准确客观地评估极重度感音神经性聋患者耳蜗残余听功能,且是人工耳蜗植入术前听力学评估方法的有意义的补充。     

Electrically evoked otoacoustic emissions from apical and basal perilymphatic electrode positions in the guinea pig cochlea

Stimulation of the cochlea with sinusoidal current results in the production of an otoacoustic emission at the primary frequency of the stimulus current. In this study we test the hypothesis that the wide frequency response from round window (RW) stimulation is due to the involvement of a relatively large spatial segment of the organ of Corti. Tonotopically organized group delays would be evident from perilymphatic electrode locations that restrict the spatial extent of hair cell stimulation. Monopolar and bipolar-paired stimulus electrodes were placed in perilymphatic areas of the first or third cochlear turns and the electrically evoked otoacoustic emissions (EEOAE) produced by these electrodes were compared to that from the RW monopolar electrode in the anesthetized guinea pig. Current stimuli of 35 microA RMS were swept across the frequency range between 60 Hz and 100 kHz. The EEOAE was measured using a microphone coupled to the ear canal. It was found that the bandwidth of EEOAEs from RW stimulation extended to at least 40 kHz and was a relatively insensitive to electrode location on the RW. The group delay of the EEOAE from stimulation at the RW membrane (corrected to stapes motion) was about 53 micros. First and third turn stimulations from electrode placements in perilymph near the bony wall of cochlea yielded narrower band EEOAE magnitude spectra but which had the same short group delays as for RW stimulation. A confined current (from a bipolar electrode pair) applied close to the basilar membrane (BM) in the first turn produced the narrowest frequency-band magnitude emissions and a mean corrected group delay of 176 micros for a location approximately 3 mm from the high frequency end of the BM (corresponding to about the 18 kHz best frequency location). Bipolar electrodes in the third turn scala tympani produced low pass EEOAE magnitude functions with corrected group delays ranging between approximately 0.3 and 1 ms. The average phase slopes did not change with altered cochlear sensitivity and postmortem. These data indicate that the EEOAE from RW stimulation is the summed response from a wide-tonotopic distribution of outer hair cells. A preliminary model study indicates that short time delayed emissions are the result of a large spatial distribution of current applied to perilymphatic locations possibly giving rise to "wave-fixed" emissions.     

豚鼠耳蜗神经活动的频谱特征

目的了解清醒状态下豚鼠耳蜗神经电生理活动的平均功率谱（Ａｖｅｒａｇｅｓｐｅｃｔｒｕｍｏｆｅｌｅｃｔｒｏｐｈｙｓｉｏｌｏｇｉｃａｌｃｏｃｈｌｅｏｎｅｕｒａｌａｃｔｉｖｉｔｙ,ＡＳＥＣＡ）的正常特征及观察耳蜗不同状况下ＡＳＥＣＡ的变化。方法采用园窗慢性电极记录耳蜗神经电活动,通过ＦＦＴ变换获得ＡＳＥＣＡ。结果在安静条件清醒状态下豚鼠ＡＳＥＣＡ图为在低频１００Ｈｚ附近有一最大的能量峰,紧接着靠近５００Ｈｚ处的为一谱谷以及中心频率为１ｋＨｚ的宽谱峰（ＡＳＥＣＡ—１ｋＨｚ）。镇静剂、麻醉剂及电极植入手术均对ＡＳＥＣＡ产生影响。结论本研究表明ＡＳＥＣＡ１ｋＨｚ为ＡＳＥＣＡ的正常特征,且３６ｄＢ（ｒｅ１ｎＶ）为ＡＳＥＣＡ１ｋＨｚ幅值的正常低限值。     

Auditory nerve neurophonic recorded from the round window of the Mongolian gerbil

In the Mongolian gerbil, round window (RW) recordings of averaged responses to phase-locked acoustic stimuli which are not alternated in polarity can include both the cochlear microphonic (CM) and auditory nerve neurophonic (ANN). The ANN can dominate the recordings when the RW electrode is referenced to some portion of the body that allows the two electrodes to straddle the auditory nerve. Concentric bipolar RW electrodes are biased in favor of the CM. When there is a substantial ANN component in the RW response, as the sinusoidal stimulus intensity increases there is a non-monotonic increase of amplitude and a pronounced change of phase of the response. When the phase-locked stimuli are alternated in polarity in order to cancel the CM, a residual response is often observed. This residual response has twice the frequency of the stimulus and is decreased in amplitude by forward masking. It also shows a pattern of amplitude decrement following the stimulus onset, resembling adaptation of firing rate of cochlear nerve axons. Tetrodotoxin (TTX) eliminates the non-monotonic RW amplitude input-output (I/O) function, reduces the phase changes of the response as the stimulus intensity is increased, eliminates the residual non-canceled response to alternated stimuli, and the time-limited amplitude decrements which resemble adaptation. Following application of TTX, the RW response of the gerbil to stimuli with non-alternated polarity much more closely resembles the CM responses of other animals. It is concluded that the gerbil's residual response following cancellation of the CM is the ANN, and that the RW of the gerbil is a convenient site for recording measures of phase-locked cochlear axonal activity.     

K(+) currents produce P(1) in the RW CAP: evidence from DC current bias, K(+) channel blockade and recordings from cochlea and brainstem

Tone-burst-evoked compound action potentials (CAP) from the guinea pig round window (RW) are altered by DC current injection through the RW. The CAP waveform consists of a series of interleaved negative and positive peaks (N₁, P₁, N₂, P₂ etc.) of decreasing amplitude. During positive DC current injection (around +50 μA) the positive peaks are depressed substantially and there is an overall negative baseline shift of the waveform following the N₁. Negative current injection (around −50 μA) increased the positive peaks, in particular P₁, and produced an overall positive baseline shift following the N₁ peak. Results support our hypothesis that the first and dominant N₁ peak in the RW CAP is due to depolarising Na⁺ currents into the primary afferent dendrites and axons within the cochlea, and that the P₁ potential is largely due to the exit of the hyperpolarising K⁺ currents in the same cells. We have reached this conclusion on the basis of the sign and latency of the N₁ and P₁ components at the RW, beneath the myelin layers around the spiral ganglion cells, at the internal auditory meatus (IAM) within the brain case, and on the basis of the differential susceptibility of the various peaks to perfusion of lidocaine in the cochlear nucleus, sectioning of the cochlear nerve at the IAM, application of the K⁺ channel blockers 4-amino-pyridine and tetraethylammonium within the cochlea, and DC current biasing at the RW.     

Inner ear disturbances following inoculation of endotoxin into the middle ear

Inner ear function was assessed by a frequency-specific (+/-100 Hz) auditory brainstem response (ABR) technique after a single instillation of a suspension of purified E. coli lipopolysaccharide in sterile water into the round window (RW) niche in rats. Instillation of endotoxin caused a transient concentration and tonotopically dependent dysfunction of the inner ear. The largest threshold impairment occurred in the high-frequency region anatomically located close to the RW. At 31.5 kHz the threshold impairment persisted throughout the study. Morphologic damage to the inner ear was not detected at the light microscopic level when using serial sections from decalcified specimens. Our study supports the clinical hypothesis that remnants of non-viable bacteria such as endotoxins, when trapped in the middle ear, can promote middle ear effusion and dysfunction of the inner ear.     

Transient focal cooling at the round window and cochlear nucleus shows round window CAP originates from cochlear neurones alone

We have measured the compound action potential (CAP) evoked by very brief high-frequency tone-bursts (20 kHz, 1/4 ms) at the round window (RW) and at the surface of the cochlear nucleus (CN) in guinea pigs before, during and after a localised chilling of either the cochlea or CN, with a non-toxic ‘freeze spray’. CN chilling almost abolished the negative-going component of the CAP measured in the CN (generated by the CN and here called the cochlear nucleus response or CNR), leaving a positive-going localised response from the cochlear neurones as they leave the internal auditory meatus. Within 3 min, the CNR recovered to control values. During that time, the N₁ component of the RW CAP was slightly increased and the P₁ was larger, even though the CNR was abolished, indicating that the P₁ was not due to electrotonic spread of current from the CN. The N₂ and successive peaks at the RW were also abolished, but returned after 30 s. When the cochlea was chilled, the RW CAP was initially reduced in amplitude, presumably due to a drop in the number of cochlear neurones spiking in response to sound, but recovered within 3 min to be larger than the control waveform, with a more prominent N₁ peak which was delayed slightly, making the CAP more monophasic. At the same time, the CNR was smaller, presumably due to fewer cochlear neurones responding, but overall the CN CAP was altered little in waveshape. These experiments indicate that that RW CAP is generated almost solely by cochlear neurones. We also suggest that some of the changes in the RW CAP during the chills were due to changes in the firing of the lateral olivo-cochlear system of efferent neurons.     

Frequency-dependence of early auditory evoked responses in the guinea pig

Summary Neural auditory responses in the guinea pig, monitored by surface electrodes (brain stem potentials and frequency-following responses) and by electrodes at the round window, were analyzed for evidence of frequency dependence in the range from 500 Hz to 15 kHz. The characteristics of the brain stem potentials and frequency-following responses with stimuli near threshold intensity for frequencies below 2 kHz indicate that this activity derives from the excitation of apical regions of the basilar membrane. The same interpretation applies to the potentials recorded at the round window. Comparison of the responses seen with surface electrodes and those appearing at the round window reveals that the broad potential P_I of the brain stem response to low-frequency stimuli corresponds to the compound action potential, while the frequency-following responses correspond to phase-locked responses in the acoustic nerve.     

Responses of auditory nerve fibers innervating regenerated hair cells after local application of gentamicin at the round window of the cochlea in the pigeon.

Hair cells in the basilar papilla of birds have the capacity to regenerate after injury. There is also functional recovery of hearing after regeneration of the hair cells. The present study was undertaken to determine the effect of local aminoglycoside application on the physiology of auditory nerve fibers innervating regenerated hair cells. Collagen sponges loaded with gentamicin were placed at the round window of the cochlea in adult pigeons. The local application of gentamicin-loaded collagen sponges resulted in total hair cell loss over at least the basal 62% of the basilar papilla. According to the pigeon cochlear place-frequency map (Smolders, Ding-Pfennigdorff and Klinke, Hear. Res. 92 (1995) 151-169), frequencies above 0.3 kHz are represented in this area. Physiological data on single auditory nerve fibers were obtained 14 weeks after gentamicin treatment. The response properties showed the following characteristics when compared to control data: CF thresholds (CF = characteristic frequency) were elevated in units with CF above 0.15 kHz, sharpness of tuning (Q10dB) was reduced in units with CF above 0.38 kHz, low-frequency slopes of the tuning curves were reduced in units with CF above 0.25 kHz, high frequency slopes of the tuning curves were reduced in units with CF above 0.4 kHz, spontaneous firing rate was reduced in units with CF above 0.38 kHz, dynamic range of rate-intensity functions at CF was reduced in units with CF above 0.4 kHz and the slopes of these rate-intensity functions were elevated in units with CF above 0.4 kHz. Maximum discharge rate was the only parameter that remained unchanged in regenerated ears. The results show that the response properties of auditory nerve fibers which innervate areas of the papilla that were previously devoid of hair cells are poorer than the controls, but that action potential generation in the afferent fibers is unaffected. This suggests that despite structural regeneration of the basilar papilla, functional recovery of the auditory periphery is incomplete at the level of the hair cell or the hair cell-afferent synapse.     

Tinnitus suppression by low-rate electric stimulation and its electrophysiological mechanisms

Tinnitus is a phantom sensation of sound in the absence of external stimulation. However, external stimulation, particularly electric stimulation via a cochlear implant, has been shown to suppress tinnitus. Different from traditional methods of delivering speech sounds or high-rate (>2000?Hz) stimulation, the present study found a unique unilaterally-deafened cochlear implant subject whose tinnitus was completely suppressed by a low-rate (<100?Hz) stimulus, delivered at a level softer than tinnitus to the apical part of the cochlea. Taking advantage of this novel finding, the present study compared both event-related and spontaneous cortical activities in the same subject between the tinnitus-present and tinnitus-suppressed states. Compared with the results obtained in the tinnitus-present state, the low-rate stimulus reduced cortical N100 potentials while increasing the spontaneous alpha power in the auditory cortex. These results are consistent with previous neurophysiological studies employing subjects with and without tinnitus and shed light on both tinnitus mechanism and treatment.     

Role of mannitol in reducing postischemic changes in distortion-product otoacoustic emissions (DPOAEs): a rabbit model

OBJECTIVES: The aim of this study was to observe the effects of mannitol, administered topically at the round window (RW), on cochlear blood flow (CBF) and distortion-product otoacoustic emission (DPOAE) after repeated episodes of cochlear ischemia. METHODS: Ten young rabbits were used for this study. Reversible ischemic episodes within the cochlea were induced by directly compressing the internal auditory artery (IAA). CBF was measured using a laser-Doppler (LD) probe positioned at the RW niche. DPOAEs were measured at 4, 8, and 12 kHz geometric mean frequency (GMF) using 60 dB sound pressure level (SPL) primary tone stimuli. In five test ears, mannitol was administered topically at the RW for 30 minutes before the IAA compressions. In five control ears, the IAA compressions were undertaken without application of RW medication. Each ear underwent three 5 minute IAA compressions with a 60 minute rest period between compressions. RESULTS: In the control animals, it was observed that a progressive reduction in DPOAE level followed each successive IAA compression at all three test frequencies. The reduction in DPOAE amplitudes was consistently greater at the higher test frequencies. In the test rabbits, the RW administration of mannitol resulted in significantly less reduction in DPOAE level measures after repeated IAA compressions. For example, 30 minutes after reperfusion at 12 kHz GMF, DPOAE levels in the control ears were reduced by 1.5, 6.0, and 16 dB, compared with 1.5, 4.0, and 6.0 dB in the mannitol test ears. CONCLUSIONS: Mannitol appears to exert a protective effect on cochlear function after periods of ischemia. The RW appears to be an efficacious route for topical administration of mannitol into the inner ear.     

Hydrocortisone applied into the round window niche causes electrophysiological dysfunction of the inner ear

A suspension of 2% hydrocortisone, micronized in sterile water, was instilled through a perforation in the tympanic membrane into the round window (RW) niche of 9 healthy rats once a day for 5 consecutive days. Three animals were used as controls, and were exposed to sterile water only instilled into the RW niche. Auditory brainstem response (ABR) thresholds were determined for eight frequencies: 2, 4, 6, 8, 12, 16, 20 and 31.5 kHz. Hydrocortisone caused impaired ABR thresholds in the frequency range of 12-31.5 kHz after 5 days of instillation. The impaired thresholds remained unchanged for 2 months, indicating irreversible electrophysiological changes in the inner ear. No morphological damage could be detected in the cochlea by means of light microscopy or transmission electron microscopy. However, hydrocortisone delayed the healing of the perforated tympanic membrane.     

Hyaluronan applied to lesioned round window membrane is free from cochlear ototoxicity

Hyaluronan (HYA) in 1% solution was instilled into the round window (RW) niche of rats (n = 6) prior to perforating the round window membrane (RWM). Cochlear functioning and structure were then monitored by recording auditory brainstem responses (ABRs) at 2-31.5 kHz and by scanning electron microscopy. Perforation of the RWM alone (n = 6) resulted in immediate loss of ABR thresholds between 6 and 31.5 kHz in 2 of 6 animals. Similar results were obtained after instilling HYA into the RW niche and subsequent RWM perforation (n = 6). After 2 months, ABR thresholds were recorded at all frequencies in the HYA-treated animals, whereas in 2 of the controls no ABR thresholds could be elicited at 20 and 31.5 kHz. However, in both treatment groups the mean ABR thresholds and mean latencies for wave II at the ABR threshold returned to the pre-surgical (normal) range after 2 months. With respect to the cochlear morphology the results in both treatment groups were also alike including minor structural changes in hair cell stereociliae but no loss of hair cells. It is concluded that HYA, when instilled into the middle ear with the inner ear opened, is free from cochlear otoxicity.     

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.     

Determinants of the spectrum of the neural electrical activity at the round window: transmitter release and neural depolarisation

In this paper we summarise the changes we have observed in the electrical activity at the round window (RW) of guinea pigs during transient cooling of the RW or cochlear nucleus (CN), transient hypoxia, low frequency acoustic biasing, ablation of the CN, and DC current injection into the basal cochlear turn. We have measured the compound action potential (CAP), the spectrum of the average CAP waveform (SAW) evoked by brief tone-bursts, and the spectrum of the neural noise (SNN). We discuss how the changes we have observed can be understood in terms of changes in transmitter release from inner hair cells (that controls stochastic neural firing), or changes in the membrane potential of the primary afferent neurones (that controls the neural firing waveshape and the spectral content of the SAW and SNN). We note that changes in sound intensity produce a simple increase in the stochastic release of transmitter from inner hair cells, without much change in the waveform of the neural response, but manipulations of the auditory brainstem, cooling and current injection all appear to alter neural firing rate and the neural response waveform, producing a baseline shift in the CAP and changes in 1000 Hz peak and low frequency content of the SAW and SNN. We also discuss the use of the CAP, SAW and SNN as an indication of cochlear and auditory brainstem neural activity.     

Chronic Reduction of Endocochlear Potential Reduces Auditory Nerve Activity: Further Confirmation of an Animal Model of Metabolic Presbyacusis

Gerbils aged in quiet show a decline of the endocochlear potential (EP) and elevated auditory nerve compound action potential (CAP) thresholds. However, establishing a direct relationship between an age-related reduction in the EP and changes in the activities of primary auditory neurons is difficult owing to the complexity of age-related histological changes in the cochlea. To address this issue, we developed a young gerbil model of “metabolic” presbyacusis that uses an osmotic pump to deliver furosemide into the round window niche for 7 days, resulting in a chronically reduced EP. In this model, the only major histopathologic changes were restricted to the hook region of the cochlea and consisted of loss of strial intermediate cells and massive edema in the lateral wall. The morphological and physiological evidence suggests that the cochlea can adapt to furosemide application over time. The morphology of spiral ganglion cells and hair cells appeared normal throughout the cochlea. CAP responses and EP values in this model are similar to those of quiet-aged ears. The spontaneous activity of single auditory fibers (n = 188) was assessed in 15 young gerbils treated with furosemide for 7 days. The percentage of recorded low-spontaneous rate (SR) fibers at characteristic frequencies (CFs) ≥ 6 kHz was significantly lower in furosemide-treated than in control ears. Recovery function tests of CAP responses after prior stimulation also showed a decline in activity of the low-SR population with CFs ≥ 6 kHz in the treated cochleas. A similar loss in the activity of low-SR fiber has been previously shown in quiet-aged gerbils. These results suggest that dysfunction of the cochlear lateral wall and subsequent chronic reduction in the EP can directly affect the activity patterns of primary auditory neurons in a manner similar to that seen in aged gerbils.     

Timing of neural excitation in relation to basilar membrane motion in the basal region of the guinea pig cochlea during the presentation of low-frequency acoustic stimulation

In spite of many studies concerning auditory nerve action potentials, the timing of neural excitation in relation to basilar membrane (BM) motion is still not well understood. In this study, therefore, BM vibrations in the basal region of the guinea pig cochlea were measured using a laser Doppler velocimeter, and action potentials in auditory nerve fibers were recorded by a conventional microelectrode technique. An attempt was then made to determine the relationship between BM motion and neural excitation in auditory nerve fibers. To obtain BM responses in the high-characteristic frequency (CF) region (18-22 kHz) and responses of auditory nerve fibers with high CFs (14-22 kHz), low-frequency stimuli (50-2000 Hz), frequencies of which were well below CFs, were presented at 60-100 dB SPL. The results indicated that neural excitation occurred when the BM was displaced toward the scala vestibuli. Moreover, the neural excitatory phase did not significantly vary with the fiber's CF between 14 and 22 kHz nor with the stimulus level between 60 and 100 dB SPL.