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The normal summating potential recorded from external ear canal.

With a "plastic leaf" electrode, cochlear summating potential (SP) and auditory nerve action potential (AP) responses to rectangular-pulse clicks were recorded from the ear canal skin surface of 96 normal-hearing ears of 48 subjects. The main goals of this investigation were to develop a more precise characterization of the relationship between SP and AP amplitudes across normal ears and to determine the confidence limits of this relationship so that a more accurate "normal limit" could be established for clinical testing. The results suggest that the across-subjects SP-AP amplitude relationship is linear. Also, SP scatter increases as AP amplitude increases, but the scatter is equalized by log transforming the data. The distance of the SP from the log-transformed SP-AP estimating line in SE ("AP-normalized SP amplitude") was found to be superior to the SP/AP amplitude ratio as a method of adjusting SP to AP amplitude, because the SP/AP ratio varied significantly with AP amplitude both across subjects and with different ear canal electrode positions.

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Effects of L-aspartate and oxaloacetic acid on click-evoked cochlear potentials.

The scala tympani of the guinea pig was perfused with artificial perilymph and experimental solutions using an electrical micropump. In test perfusions, 20 mM L-aspartate produced depression of APN1 by 49% and 25 mM L-aspartate decreased the amplitude of APN1 by 42%. Both 20 mM and 25 mM L-aspartate were without effect on the CM, the latency or width of APN1. Perfusions with 10 mM oxaloacetic acid were without effect on the APN1 and CM. In our previous experiments, 5 mM L-aspartate had no effect on APN1 and CM, but 10 mM L-aspartate or 15 mM L-aspartate introduced into the scala tympani reversibly increased the amplitude of APN1 and CM. It is concluded that L-aspartate may have a modulating influence on signal transmission of afferent synapses in the cochlea.

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Distortion products in early stage experimental hydrops in the guinea pig.

The swelling of the endolymphatic spaces in experimental hydrops is likely to induce mechanical changes all along the cochlea. The selective atrophy of short and middle stereocilia on the outer hair cell above the first cochlear turn is expected to alter micromechanics and transduction. Two tone stimuli were employed in the present study to investigate cochlear distortion products in hydropic ears. Despite a substantial low frequency sensitivity loss on the CAP audiogram, 2f1-f2 distortion products recorded in the RWCM and the CAP were similar in hydropic ears and normal control ears which reflect the probable common origin of these responses--the base of the cochlea where no threshold shifts can be detected. On the other hand this distortion product in the otoacoustic emissions was considerably reduced in hydropic cochleas when the primary tones lay within the pathological part of the audiogram. The reduction of CDT emissions cannot be accounted for by hair cell loss since at the early stage of hydrops described here there is only discrete hair cell loss which is restricted to the apex of the cochlea. On the other hand the reduction in the amplitude of the CDT might reflect disturbance in hair cell function and/or cochlear mechanics above the first cochlear turn.

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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 mirophonic (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 the 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.

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Effect of artificial endolymph injection into the cochlear duct on the endocochlear potential.

We investigated the effect of acute endolymphatic hydrops on the positive endocochlear potential (+EP) and negative endocochlear potential (-EP). The +EP was measured in guinea pigs during injection (without outlet) and perfusion (with outlet) of artificial endolymph into the cochlear duct. The -EP was measured during anoxia after the injection or the perfusion had finished. Injection of artificial endolymph produced a slight transient increase in the +EP, and a significant decrease in the magnitude of the -EP. Chronic endolymphatic hydrops produces both +EP and -EP decrease. The +EP decrease in chronic endolymphatic hydrops may cause the chronic change of the inner ear. The +EP increase in acute endolymphatic hydrops may be caused by a shift of the basilar membrane. However, the mechanism of the 'transient' +EP increase is not clear. The -EP decrease was not observed in animals whose cochlear duct was perfused with artificial endolymph. Therefore, the artificial endolymph itself did not cause the decrease in magnitude of the -EP. Dysfunction of the hair cells is a possible explanation for the -EP decrease but the mechanism of such a decrease is not clear in the present study. However, the results of this study support the notion that small increases in endolymphatic pressure below the resolution of recent measurements (DeMott and Salt, 1997) can lead directly to a reduction of the -EP during hydrops. The animal model described here can eliminate the chronic effect of hydrops, therefore, this model is useful for investigations into the effect of hydrops itself on the inner ear and the mechanism of hearing loss in Ménière's disease.

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Receptor potentials of lizard cochlear hair cells with free-standing stereocilia in response to tones.

Intracellular potentials were recorded with micropipettes from hair cells with free-standing stereocilia in the cochleae of anaesthetized alligator lizards. Wave forms of intracellular responses to click stimuli were classified into three types: hair cells, supporting cells, and untuned cells. We studied primarily the responses of hair cells to tonal stimuli. For most frequencies, f, and levels, P, of tone-burst stimuli, the response envelope of the receptor potential increases monotonically at the tone-burst onset, and decreases monotonically at tone-burst offset. Overshoot in the envelope of the response at the onset and offset of tone bursts is observed only for tone bursts of low f, high P, and short (approximately equal to 1 msec) rise/fall time. The steady-state response to tones consists of a positive (depolarizing) d.c. component, V0, plus a.c. components (e.g. a fundamental component, V1, second harmonic, V2, and third harmonic, V3). The magnitudes of a.c. and d.c. components are functions of f and P, and show three characteristics: frequency selectivity, non-linearity, and low-pass filtering. The receptor potential is frequency selective. The frequency selectivity of V0 and V1 components was measured by means of iso-voltage (iso-V0 and iso-V1) contours. Iso-V0 and iso-V1 contours are V-shaped: the maximum sensitivity occurs at a characteristic frequency (c.f.). The shapes of these contours near the c.f. depend on the values of V0 and V1 at which the contours were measured and are sharper for lower values of V0 and V1. The mean slopes of the low- and high-frequency sides of these contours are: -45.0 and +85.1 dB/decade for iso-V0 contours (n = 26), and -33.6 and +103.8 dB/decade for iso-V1 contours (n = 28). The receptor potential has non-linear properties. The magnitudes and phase angles of V0, V1, V2, and V3 receptor-potential components were measured as a function of P for different f. The slopes of level functions (the dependence of log V0 and log magnitude of V1 on log P) were measured at low levels for different f. For values of f differing from c.f. by more than a half-octave, the slope for V0 is between 1 and 2 with a mean of 1.3; the slope for V1 is about 1, i.e. magnitude of V1 increases approximately linearly with P. For frequencies near c.f., the slopes for V0 and V1 are approximately 0.8 and 0.5, respectively, indicating the presence of a compressive non-linearity.(ABSTRACT TRUNCATED AT 400 WORDS)

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Frequency selectivity of hair cells and nerve fibres in the alligator lizard cochlea.

Receptor potentials of hair cells and spike discharges of cochlear nerve fibres were recorded with micropipettes from the free-standing region of the basilar papilla of anaesthetized alligator lizards in response to tones. In this region the hair-cell stereocilia are free-standing, i.e. they protrude directly into endolymph and are not in contact with a tectorial membrane. The frequency selectivity of hair-cell responses was measured by means of isovoltage contours of the d.c. (V0) and fundamental-a.c. (V1) component of the receptor potential, i.e. iso-V0 and iso-V1 contours. The frequency selectivity of the nerve-fibre discharge was measured by iso-rate (iso-V0) contours. Iso-V0, iso-V1 and iso-V0 contours are basically V-shaped with a characteristic frequency (c.f.) defined as the frequency at which minimum sound pressure (Pmin) is required to evoke the criterion value of the response. Receptor potential iso-V0 contours and neural iso-V0 contours have similar slopes: the mean slopes of the low-frequency sides (dB/decade) are -43.0 and -44.3; the slopes of the high-frequency sides are 85.0 and 80.2. The band widths of iso-V0 and iso-V0 contours away from c.f. are similar (mean values of Q30dB are 0.40 and 0.53, respectively). The band widths of iso-V0 contours near c.f. are narrower than those of iso-V0 contours (mean values of Q10dB are 2.34 and 1.20, respectively). However, the shapes of the contours near c.f. depend on the iso-response criteria, and we have not determined whether or not iso-V0 and iso-V0 contours are similar near c.f. The shapes of iso-V1 contours differ from those of iso-V0 and iso-V0 contours. Nerve fibre c.f.s are tonotopically organized in the nerve, with lowest c.f.s recorded from fibres innervating the border of free-standing and tectorial regions, a region in which hair-cell stereocilia are longest, and the highest c.f.s recorded from fibres innervating the end of the free-standing region in which hair-cell stereocilia are shortest. The c.f. of nerve-fibre response (and by implication hair-cell response) is, therefore, correlated with the height of the stereociliary tuft. The shapes of iso-V0 contours vary systematically with c.f. and, therefore, tonotopically with nerve position.(ABSTRACT TRUNCATED AT 400 WORDS)

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N1 latency prolongation in the guinea pig cochlea treated with nitrogen mustard-N-oxide studied by narrow band analysis.

The effect of nitrogen mustard-N-oxide (NMO) upon the click and tone burst-evoked N1 latency was examined in 14 albino guinea pigs. In all animals except one, the pseudothresholds of action potentials were elevated, especially in the high tone area. In addition to the amplitude reduction, the N1 latency was prolonged in 12 animals. The narrow band analysis of N1 revealed that the latency was equally prolonged in all frequency areas, although the amount of the amplitude reduction was much larger in the high frequency area. It was concluded that the prolongation of the N1 latency in NMO-treated animals was due to dysfunction of outer hair cells along the entire cochlear partition.

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Role of perilymphatic fistula in sudden hearing loss: an animal model.

The electrophysiologic response of the guinea pig cochlea was monitored after sequential lesions to Reissner's membrane and the round window (RW). Action potential (AP) responses to click stimuli were recorded from the RW before and after discrete puncture-type lesions were created in the cochlear partition of the second turn. Observed decrements were typically minor, comparable to no greater than 10 dB attenuation of stimulus intensity. The RW membranes then were perforated to create perilymphatic fistulas. Further monitoring demonstrated a rapid (within 5 to 10 minutes), severe decrement in AP amplitude and latency, with complete loss of the AP within 1 hour. Control animals with RW perforations alone did not show these decrements. Correct placement of the second turn lesions was documented by histology. We conclude that discrete lesions in the cochlear duct are not reflected in the AP input-output functions unless there is a fluid leak from the RW, and thus present a possible model for idiopathic sudden hearing loss.

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Effects of kanamycin sulfate on cochlear potentials and potassium ion permeability through the cochlear partitions.

The cochlear microphonics (CM), endocochlear potential (EP) and potassium ion activities in the endolymph and perilymph were measured in guinea pigs which received daily successive intramuscular injections of 500 mg/kg of body weight of kanamycin sulfate. Preyer's reflex threshold at 8 kHz began to increase after the 5th day of kanamycin treatment and disappeared on the 11th day. The maximum output of CM at 8 kHz began to decrease with a time course similar to Preyer's reflex. The potassium ion activities in the endolymph and perilymph and the EP did not change appreciably through all experimental days. The magnitude of the negative EP decreased in parallel with the reduction in CM and the relative potassium conductance (GK) between the endolymph and perilymph. These results lend support to the hypothesis that the site of production of the negative EP is probably in the hair cells and that the negative EP is mainly dependent on the permeability of the potassium ions in the organ of Corti.

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Otoacoustic emissions without somatic motility: can stereocilia mechanics drive the mammalian cochlea?

Distortion product otoacoustic emissions (DPOAEs) evoked by low-level tones are a sensitive indicator of outer hair cell (OHC) function. High-level DPOAEs are less vulnerable to cochlear insult, and their dependence on the OHC function is more controversial. Here, the mechanism underlying high-level DPOAE generation is addressed using a mutant mouse line lacking prestin, the molecular motor driving OHC somatic motility, required for cochlear amplification. With prestin deletion, attenuated DPOAEs were measurable at high sound levels. DPOAE thresholds were shifted by approximately 50 dB, matching the loss of cochlear amplifier gain measured in compound action potentials. In contrast, at high sound levels, distortion products in the cochlear microphonic (CM) of mutants were not decreased re wildtypes (expressed re CM at the primaries). Distortion products in both CM and otoacoustic emissions disappeared rapidly after death. The results show that OHC somatic motility is not necessary for the production of DPOAEs at high SPLs. They also suggest that the small, physiologically vulnerable DPOAE that remains without prestin-based motility is due directly to the mechanical nonlinearity associated with stereociliary transduction, and that this stereocilia mechanical nonlinearity is robustly coupled to the motion of the cochlear partition to the extent that it can drive the middle ear.

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Experimental basis for lidocaine therapy in cochlear disorders.

In order to further our basic understanding of the effects of lidocaine hydrochloride in the inner ear, cochlear potentials and blood flow (CBF) were assessed after intravenous (i.v.), anterior inferior cerebellar artery (AICA), and local round window (RW) lidocaine administrations in guinea pigs and rats. Lidocaine RW applications produced a dose dependent decrease in compound action potentials (CAP) and cochlear microphonics (CM). The sensitivity changes were more pronounced at high frequencies. These findings suggest that lidocaine has specific pharmacological action in the inner ear other than simple anesthesia of the auditory nerve. The basal turn endocochlear potentials (EP) were not altered by topical lidocaine, implicating altered organ of Corti function following local application of lidocaine. RW applications of lidocaine had no effect on CBF or systemic blood pressure (BP). I.v. infusions caused substantial reductions in BP. In the case of systemic infusions the percent changes in CBF were equal to and accountable by the BP changes. The microinfusions (50 mg/ml, 100 nl/min) through AICA produced a 30%, long lasting increase in CBF. However, neither systemic lidocaine nor AICA infusions had an effect on CAP or CM. These findings indicate that systemically given lidocaine may not cross the blood-cochlear barrier and that the cochlear electrophysiological effects due to lidocaine when given locally are partly mediated by direct influence on cochlear hair cell function; they also suggest that lidocaine-induced interference with active ion transport in the lateral wall or an influence on CBF are not contributing factors.

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Differential vulnerability of inner and outer hair cell systems to chronic mild hypoxia and glutamate ototoxicity: insights into the cause of auditory neuropathy.

OBJECTIVE: To describe the effects of long-term mild hypoxia and of glutamate poisoning on the functional properties of the cochlea. METHODS: Outer hair cell activity was monitored using otoacoustic emissions and cochlear microphonics, and inner hair cell/cochlear afferent function was measured using neural responses (cochlear action potentials or auditory brainstem responses [ABRs]). RESULTS: In contrast to the effects of acute anoxia, in which all aspects of cochlear function are simultaneously lost, mild, long-term hypoxia results in a clear differential effect on outer versus inner hair cell systems. During a 2-hour period of mild hypoxia, ABR amplitude and threshold deteriorate significantly, whereas outer hair cell function, as reflected by otoacoustic emissions, shows little or no change. A similar dissociation between inner and outer hair cell function is observed during instillation of glutamate (1-10 mM), where the cochlear microphonic and the otoacoustic emissions are unchanged, whereas cochlear action potential amplitudes are reduced. CONCLUSION: These studies demonstrate a difference in vulnerability of inner and outer hair cell systems. The inner hair cell/cochlear afferent system is vulnerable to long-term, mild hypoxia; this may be an etiologic factor in hearing loss of cochlear origin, particularly in high-risk birth infants with auditory neuropathy.

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Basilar membrane mechanics at the base of the chinchilla cochlea. II. Responses to low-frequency tones and relationship to microphonics and spike initiation in the VIII nerve.

Low-frequency stimuli (40- to 1000-Hz tones) have been used to correlate the motion of the 8-to 9-kHz place of the chinchilla basilar membrane with the cochlear microphonics recorded at the round window and with the responses of auditory nerve fibers with appropriate characteristic frequency. At the lowest stimulus frequencies, maximum displacement of the basilar membrane toward scala tympani occurs in near synchrony with maximum rarefaction at the eardrum and maximum negativity at the round window; at higher frequencies, the mechanical and microphonic response phases progressively lag rarefaction, reaching - 240 deg at 1000 Hz. At most frequencies (40-1000 Hz) near-threshold neural responses, once corrected for neural travel-time and synaptic delays, somewhat lead (by some 40 deg) maximal scala tympani displacement and maximal negativity of the round window microphonics. The variation of sensitivity with frequency is similar for basilar membrane displacement and microphonic responses: Under open-bulla conditions, sensitivity is constant for frequencies between 100 and 1000 Hz; below 100 Hz, sensitivity decreases at rates close to 12 dB/oct toward lower frequencies. Neural response sensitivity matches BM displacement more closely than BM velocity.

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