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A monaural space map in the guinea-pig superior colliculus.

Under anechoic conditions, a horizontal array of loudspeakers was used to investigate the representation of auditory space in the guinea-pig superior colliculus. We have previously demonstrated that in animals with both ears intact, there is a topographical representation of the azimuthal dimension of auditory space in the deep layers of this nucleus. In the present study, we have investigated the contribution of monaural and binaural cues to the generation of the auditory space map. Occlusion of one ear or unilateral cochlear destruction resulted in omnidirectional responses in all cells to white-noise stimuli more than 20 dB suprathreshold. The sensitivity of cells to the location of sound at or near threshold was, however, unchanged and we demonstrate the presence of a threshold, monaural auditory space map. This monaural space map was destroyed by removal of the contralateral pinna and concha which resulted in all cells responding best, at threshold, to sounds opposite the external auditory meatus. Measurements of cochlear microphonic (CM) potentials, although variable, revealed that the pinna and concha may result in location-specific changes in the spectral pattern at the tympanic membrane.

Animals↗

The effects of hyperbaric oxygen on experimental noise damage to the ears.

The effect of hyperbaric oxygen on cochlear microphonics, action potential of the auditory nerve, and brain stem response damaged by short exposure to noise is varied. Of 26 guinea pigs 14 showed a positive influence as measured by amplitudes. In 12 animals oxygen had little or no effect. The reason for this could lie in the individual reaction to the anesthetic of the section of the auditory nerve tested. The reaction of postmortem cochlear microphonics after hyperbaric oxygen treatment indicates oxygen diffusion through the round window.

Animals↗

Cisplatin ototoxicity and the possibly protective effect of alpha-melanocyte stimulating hormone.

It is known that adrenocorticotrophic hormone (ACTH)-derived peptides, the so-called melanocortins, can reduce cisplatin-induced neurotoxicity. Recently, our group has found that cisplatin-induced ototoxicity can also be reduced or prevented by treatment with the synthetic melanocortin-like peptide, ORG 2766 (Hamers et al., 1994; De Groot et al., 1997). The present study was designed to investigate the possibly ameliorating effects of the physiologically more relevant naturally occurring neuropeptide alpha-melanocyte stimulating hormone (alpha-MSH) upon cisplatin ototoxicity and to compare its protective effects to those of ORG 2766. For eight consecutive days guinea pigs were treated with cisplatin at a concentration of either 1.5 mg/kg/day or 2 mg/kg/day. Animals were co-treated with either alpha-MSH (75 microg/kg/day), ORG 2766 (75 microg/kg/day), or a sham injection containing physiological saline. Electrocochleography and hair cell counts were performed. Treatment with 1.5 mg/kg/day cisplatin resulted in a large variability of the morphological and electrophysiological data, a variability that might have masked possible effects of ORG 2766 and alpha-MSH. Treatment with 2 mg/kg/day cisplatin caused less variable, severe reductions in the compound action potentials and cochlear microphonics combined with basal and middle-turn outer hair cell loss in five out of six animals. However, in the alpha-MSH co-treated groups, two out of six animals could be classified as normal, two animals as moderately affected and two animals as severely affected. In the ORG 2766 co-treated group we found three animals that were not affected and three animals that were severely affected. We conclude that the protective effects of alpha-MSH and ORG 2766 co-treatment are comparable and that alpha-MSH might be clinically useful in protecting against cisplatin-induced ototoxicity.

Action Potentials↗

Electrocochleography during intravenous infusion of cisplatin.

Extratympanic electrocochleography was performed on three patients following tobramycin injection and ten patients during cisplatin (cis-dichlorodiamine platinum II infusion. The compound eighth nerve action potential and the cochlear microphonic decreased considerably in magnitude up to 45 to 60 minutes after tobramycin injection, followed by a gradual recovery to normal in all three patients. During the eight hours of continuous cisplatin infusion, there was no significant change in the eighth nerve action potential and cochlear microphonic. The immediate effect of tobramycin on the cochlear output may be due to interference with the metabolism of the inner ear by the drug. The absence of electrocochleographic change during cisplatin infusion may be due to differences in the mechanism between cisplatin and aminoglycoside ototoxicity, or it may reflect the relatively nonototoxic potential of our chemotherapy regimen.

Adolescent↗

Clinical monitoring of the effects of gentamicin by electrocochleography.

Eight patients receiving prolonged treatment with gentamicin for bacterial endocarditis were monitored for possible ototoxicity using transtympanic electrocochleography as an adjunct to pure tone audiometry, vestibular function tests and serum gentamicin levels. An immediate effect of intravenous gentamicin on the cochlea, shown by changes in the whole nerve action potential and/or cochlear microphonic was recorded in seven patients, none of whom had experienced vestibular or auditory symptoms with gentamicin prior to testing. Two patients subsequently developed evidence of vestibular dysfunction, and a high frequency sensorineural hearing loss occurred in a third individual. There have been no previous report of the immediate effects of gentamicin on the human cochlea to date. The significance of these findings in routine clinical monitoring of ototoxicity is discussed in the light of clinical and animal evidence for the possible mode of action of aminoglycosides on the auditory and vestibular apparatus.

Action Potentials↗

Substance P increases cochlear blood flow without changing cochlear electrophysiology in rats.

Carotid artery infusions of substance P yielded reductions in systemic blood pressure and elevations in cochlear blood flow (CoBF), measured via laser Doppler flowmeter, with no alterations in cochlear action potentials or cochlear microphonics in Wistar-Kyoto rats. Additionally, direct micro-infusions of substance P into the anterior inferior cerebellar artery, which contributes to the local vascular perfusion of the cochlea, yielded elevations in CoBF with no changes in systemic blood pressure. Pretreatment with a specific substance P receptor antagonist, ([D-Pro2,D-Trp7,9]SP) via the carotid artery or the anterior inferior cerebellar artery, diminished subsequent substance P-induced vascular responses. These results suggest that endogenous substance P, like other vasoactive peptides, may interact with a substance P-specific receptor population in the cochlea and may therefore participate in the ongoing regulation of CoBF. These findings also support the premise that vasodilatory hormones, along with vasoconstrictive agents, may be involved in the autoregulation of CoBF.

Action Potentials↗

Measurements of perilymphatic oxygen tension in guinea pigs exposed to loud sound.

Using different types of custom-made oxygen-sensitive microelectrodes, the perilymphatic oxygen partial pressure (PO2) was determined in anesthetized guinea pigs. Cochlear temperature, heart rate, and arterial blood pressure and acid-base status were monitored. The PO2 in the basal scala tympani perilymph (200 microns below the round window membrane) was found to be 53 +/- 17 mmHg (mean +/- SD) in 33 normal animals. In 11 guinea pigs exposed to loud sound for 15 min (10 kHz pure tone, 125 dB SPL) there was on average a continuous decline in the perilymphatic PO2, which was significant only 30 min post-exposure. A considerable variation in response was found in individual animals. Mean arterial blood pressures showed a slightly increasing time course, while heart rates did not change significantly during the whole period of the experiment. Arterial acid-base status and PO2 values remained within normal limits and did not change significantly. Cochlear microphonics and compound action potentials were substantially decreased after acoustic overstimulation. The results are discussed with due consideration of sources of error.

Acoustic Stimulation↗

The protective effects of tirilated mesylate (U74006F) on ischemic and reperfusion-induced cochlear damage.

We have recently demonstrated that allopurinol, a blocker of free oxygen radical (FOR) production, and superoxide dismutase (SOD), a scavenger of FOR, protect the cochlea from damage associated with ischemia/reperfusion. The purpose of this present study was to determine if tirilated mesylate (U74006F), a potent inhibitor of lipid peroxidation, can also protect the cochlea from ischemia/reperfusion. Eleven Wistar-Kyoto rats were randomly assigned to two groups: (1) a control group (6 animals) that was exposed to 15 minutes of cochlear ischemia by clamping the anterior-inferior cerebellar artery (AICA), followed by 15 minutes of reperfusion, and (2) a drug-treated group (5 animals) that received U74006F before ischemia/reperfusion. In the control group, the tone burst-evoked compound action potential (CAP) recorded from the round window (RW) was abolished and cochlear microphonic (CM) was reduced. In contrast, the U74006F-treated animals showed post-reperfusion sensitivity in CAP, and less of a CM threshold shift. We interpret these results to indicate that U74006F lessens cochlear damage occurring as a result of ischemia/reperfusion and supports the hypothesis that FOR-induced lipid peroxidation may be partly responsible for the cochlear damage that occurs from ischemia.

Action Potentials↗

Target sites of polymyxin B ototoxicity.

The present study was undertaken to determine the target sites of polymyxin B ototoxicity. This drug, at the concentration of 1 mM, was perfused through the scala tympani of the guinea pig cochlea, and cochlear microphonics and endocochlear potentials were monitored. Both cochlear potentials altered but in an independent manner. These findings indicated that not only the organ of Corti but also another tissue is involved in the ototoxicity produced. The best locus for this is the vascular stria.

Animals↗

The development of auditory function in the cochlea of the mongolian gerbil.

Cochlear microphonic (CM) potentials were recorded throughout the development of auditory function in the Mongolian gerbil. CM responses were first recorded at 12 days after birth (DAB), with thresholds exceeding 103 dB SPL. CM thresholds subsequently improved rapidly in a parallel fashion across the responsive frequency range, achieving adult levels by 18 DAB. There was no evidence from CM thresholds of a preferential rate of maturation for either the high or low frequency ranges. CM responses to suptrathreshold stimulation were also studied throughout development. At all responsive ages, CM input-output functions increased logarithmically to a saturating maximum value and then declined. Maximum CM responses increased continuously throughout development in a parallel fashion across all frequencies. The dynamic range of the CM input-output functions (the intensity interval from CM threshold to maximum CM value) also developed in a parallel manner across frequencies, but reached mature assymptotic values by 16 DAB. The results suggest that throughout the adult CM frequency range cochlear hair cell function develops simultaneously.

Age Factors↗

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.

Action Potentials↗

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.

Action Potentials↗

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.

Action Potentials↗

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.

Acoustic Stimulation↗

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.

Action Potentials↗

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)

Acoustic Stimulation↗

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)

Action Potentials↗