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[Microperforation and removal of the round window membrane. Short- and long-term study in animal experiments using electrocochleography and evoked response audiometry].

Our earlier animal experiments on guinea pigs showed that instrumental perforation of the round window membrane by a 0.2 mm platinum wire leads to an instant loss of the inner ear functions. The membrane defect healed in a few days, the cochlear structures remained intact, and the compound action potential of the auditory nerve and the brain-stem responses could be evoked again with normal latency times within 2 weeks. 1. In the studies reported here we first carried out microperforations with a 1 micron needle electrode, which caused no changes of the hearing potentials (cochlear microphonics, compound action potential of the auditory nerve, brain-stem responses), and no visible defect of the round window membrane and no perilymph outflow. 2. The removal of the round window membrane and the withdrawal of the perilymph led to a loss of the cochlear microphonics and to a considerable increase of the latency times of wave I (Jewett). The hearing potential regained their original values after 2 weeks without closure of the round window niche. The round window membrane had regenerated spontaneously and the scala tympani was again filled with perilymph. After covering the round window niche with a connective tissue graft, the hearing potentials regained their original values after 2 weeks, as they had done without cover of the round window niche. The round window membrane regenerated below the tissue graft and the scala tympani was also filled again with perilymph.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Cytochalasin D suppresses sound evoked potentials in the guinea pig cochlea.

Cytochalasin D (CD), an inhibitor of actin polymerization, was perfused through the guinea pig cochlea while monitoring various cochlear potentials. CD (10(-7)-10(-5) M) reduced the magnitude of the compound action potential of the cochlear nerve and the summating potential, and increased N1 latency. The cochlear microphonic potential was the least sensitive potential with only a slight effect being observed at 10(-5) M. The results are consistent with the hypothesis that actin has a role in cochlear function.

Actins

[Narrow-band action potentials of the guinea-pig cochlea as compared with the ordinary electrocochleograms under normal and pathological conditions].

The narrow-band action potentials (NAP) and the ordinary electrocochleograms were recorded from the guinea-pig cochlea under normal and pathological conditions in order to study whether the NAP could be a useful measure to detect cochlear dysfunctions. The cochlea damaged either by the administration of kanamycin or by a mechanical lesion of the round window served as pathological materials. Recordings showed that the threshold and amplitude measured for the N1 potential of NAPs ran in parallel with those of the cochlear microphonic potentials (CM), under both normal and pathological conditions of the cochlea. This implies that the CM could be replaced by the NAP when difficulties were present in recording CMs. It may be inferred that the NAP reflects responses of the inner hair-cells and cochlear nerves, while the CM would mainly be derived from responses of the outer hair-cells to the frequency-specific movements of the basilar membrane. If so, the NAP should offer a good means for the objective audiometry. Recording NAPs is also superior to the ordinary electrocochleography in that the method makes it possible to obtain responses generated near the apex of the cochlea, i.e., responses to low-pitch sound stimuli.

Action Potentials

Sources of frequency following responses (FFR) in man.

In order to study the sources and pathways which are responsible for the frequency following response (FFR), records were made in control subjects and in patients with special types of lesion and response. It has already been shown that the FFR in normal subjects to tone bursts with single onset phases is made up of a short latency cochlear microphonic potential (CM) and a longer latency neural component (neural FFR). No neural FFR could be recorded in patients with upper brain-stem lesions (absence of click-evoked responses from the inferior colliculus along with clinical signs of such a lesion). Their FFR was exclusively a cochlear microphonic potential, thus demonstrating that the neural FFR with a latency of 6 msec is generated in the region of the inferior colliculus. Also in subjects with large post-auricular muscle (PAM) responses, the PAM can contribute to the FFR, with a latency of 10 msec. In patients with high-tone hearing loss due to acoustic trauma, no CM could be recorded while a neural FFR with a latency of 6 msec was present. This indicates that the CM recorded by this technique may be generated in the basal turn. It also demonstrates that the pathway of the neural FFR begins in the apical turn of the cochlea.

Adult

Low-frequency sensitivity in a gerbilline rodent, Pachyuromys duprasi.

The contribution of the bulla to low-frequency hearing capability was studied in the gerbilline rodent Pachyuromys duprasi. In the frequency range of 0.6-3 kHz, the sound pressure behind the tympanic membrane is higher than the pressure in the meatus acusticus externus near the eardrum. Gradual augmentation of frequencies above 0.6 kHz gives rise to steadily increasing phase lag in the bulla relative to that in the meatus. Severing of the incudostapedial joint yields results indicating that the phase difference between meatus and bulla is caused by resonance properties of the bulla and resistance in the cochlea. Both destruction of the bulla and stiffening of the pars flaccida tympani lead to a sound pressure decrease in the frequency range around 2 kHz. This drop is accompanied by an amplitude decrease of the same magnitude in the cochlear microphonic potentials. These results support the hypothesis that the bulla functions like a Helmholtz resonator in the frequency range of 1-3 kHz, improving sound transduction to the cochlea. These experimental findings, in conjunction with theoretical considerations involving bulla volume, orifice area of the resonator, and resonance frequency of the bulla, suggest that the theoretically required area of the resonator's orifice is, in fact, of the same magnitude as the area of the pars flaccida tympani. The middle-ear system of P. duprasi thus consists of a resonating bulla in which the area of the pars flaccida tympani constitutes the resonator's opening towards the meatus and in which the pars tensa tympani functions as a pressure gradient receiver, due to phase differences caused by the resistance of the cochlea and by the resonance properties of the bulla. By these functional principles the peripheral auditory system of P. duprasi is capable of low-frequency perception despite the smallness of its structures. The middle ear in P. duprasi thus represents a prime example of a strategy: the dimensional constraints derived from a general bauplan for the peripheral auditory system have here been overcome.

Animals

Electrical correlates of mechanical events in the cochlea.

In this paper the main emphasis is laid on presenting an up-to-date description of the relationships between stimulus-related cochlear potentials: cochlear microphonic (CM) and summating potential (SP) and the preceding mechanical events. To this end, CM and SP (both DIF and AVE SP) magnitude functions, obtained with the differential electrode technique, are shown from various turns of the guinea pig's cochlea as recorded at a constant stapes displacement. The similarity between these curves and corresponding basilar membrane displacement functions is considered. The influence upon CM recording of the distributed nature of the generators, as well as the presence of strong nonlinear effects is discussed.

Acoustic Stimulation

Electrophysiological evidence for the presence of NMDA receptors in the guinea pig cochlea.

An excitatory amino acid, possibly L-glutamate, which probably acts as a neurotransmitter at the inner hair cell-afferent fiber synapses in the cochlea. In the present study, we have used an electrophysiological approach to investigate at this level the presence of a major type of excitatory amino acid receptor, namely the glutamatergic receptor for which N-methyl-D-aspartate is a selective agonist. Our results show that, when N-methyl-D-aspartate and the antagonist 2-amino-5-phosphonovalerate are perfused through the perilymphatic scalae, they induced, by different mechanisms, a significant reduction of the amplitude of the compound action potential and an increase of the N1 latency, both predominant at high intensity tone burst stimulations. No significant difference was found in the presence or absence of Mg2+ in the artificial perilymph used as a vehicle. A further slight N-methyl-D-aspartate-induced decrease of the amplitude of the compound action potential, although non significant, was observed when the Mg2(+)-free perilymph contained 100 or 1000 microM glycine. In all the experimental conditions, no effect was observed on the cochlear microphonic potential. This observation is consistent with an action of N-methyl-D-aspartate and 2-amino-5-phosphonovalerate at receptors located on the auditory nerve dendrites contacting the inner hair cells. In conclusion, our results suggest the presence of N-methyl-D-aspartate receptors in the cochlea.

2-Amino-5-phosphonovalerate

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid electrophysiological and neurotoxic effects in the guinea-pig cochlea.

We have recorded cochlear potentials after perilymphatic perfusion of cumulative doses of the excitatory amino acid alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) which selectively recognizes the non-N-methyl-D-aspartate ionotropic receptor formerly known as the quisqualate receptor. Our results show that AMPA (1-80 microM) caused a significant suppression of the amplitude of the compound action potential evoked by acoustic stimulation. A total elimination of this potential at the 100 microM concentration was observed in all animals. In no case was the cochlear microphonic potential, a hair cell receptor potential, affected by AMPA. Histological examinations were performed either at the end of the physiological studies or on cochleas perfused for 10 min with a single dose of AMPA (50 or 100 microM). In both experimental conditions, a selective dendritic swelling or radial afferent nerve endings under the sensory inner hair cells was observed. No damage was found in both types of hair cells supporting cells, lateral and medial efferent fibers and spiral afferent nerve ending on the outer hair cells. The occurrence of the radial dendrite swelling was prevented when 6,7-dinitroquinoxaline-2,3-dione (500 microM) was perfused in the cochlea 10 min prior, then concomitantly with AMPA. The present study strongly suggests that non-N-methyl-D-aspartate receptors, possibly of the AMPA subtype, are involved in the synaptic transmission between the inner hair cells and the primary auditory neurons. They provide further support for the hypothesis that L-glutamate, or another excitatory amino acid, acts as an inner hair cell neurotransmitter.

Acoustic Stimulation

The effect of sectioning auditory centrifugal fibers on the cochlear microphonic and action potential in guinea pigs.

This investigation on 8 guniea pigs determined the immediate effect on the cochlear microphonic (CM) and action potential (AP) of ipsilateral sectoning of the autitory centrifugal fibers. An acoustic signal was used to evoke the CM and AP of one ear of guinea pig and the homolateral olivo-cochlear bundle and lateral lemniscus were then sectioned. Differences between pre- and post-section CM and AP were measured. The results demonstrated an increase in the CM and a decrease in the AP in all animals. Speculation with regard to the overall function of the auditory centrifugal system was offered.

Action Potentials

Effects of putative transmitters on afferent cochlear transmission.

Putative transmitters and related substances were perfused through the guinea pig scala tympani while monitoring the compound action potential of the cochlear nerve (AP) and the cochlear microphonic potential. Various substances were then ranked according to their ability to reduce the AP. The more active compounds ranked: methysergide (1 mM) greater than ATP (10 mM) = tyramine (10 mM) greater than salicylate (10 mM) greater than bicuculline (10 mM) greater than asparate (10 mM) greater than glutamate (10 mM) greater than citrate (10 mM) greater than dextrose (100 mM) greater than glycine (100 mM) greater than GABA (100 mM) greater than prostaglandin E2 (1 mM) greater than serotonin (10 mM). The activity of substances at 100 mM indicates a physical, osmotic change in the cochlear structure. Activity at 10 mM and 1 mM indicated afferent transmitter-like activity for the putative transmitters and interference with the endogenous transmitter for related substances. It is concluded that several substances can be eliminated as afferent transmitter candidates, while others warrant further examination.

Action Potentials

Coherence of frequency modulation is encoded by cochlear-generated distortion.

Nonlinearities of the peripheral auditory system generate distortion products which present to the central auditory system as apparent acoustic stimuli. The frequency and amplitude of distortion products reflect the frequency, phase and amplitude relationship of the components of a complex stimulus. When the stimulus consists of harmonically-related primaries, the amplitudes of the major distortion products are a function of the relative phase of the presented (primary) tones. We have previously shown (McAnally and Calford, 1990) that the variation of amplitude of the distortion as a function of the relative phase of a pair of harmonically-related primaries is well modelled as a function of the interaction of the multiple modes of distortion which fall at the same frequency (e.g. difference frequency and cubic difference frequency). A possibility raised by this result is that coherence of frequency modulation (that which maintains harmonicity) could be encoded in the amplitude of distortion. This was examined in measurements of both the cochlear microphonic potential (CM) and the responses of auditory nerve fibres in anaesthetized cats. Very small deviations from coherence of frequency modulation produced changes in the amplitude of the CM potential at the frequency of distortion. Also the discharges of auditory nerve fibres tuned to the frequency of distortion were found to be modulated at the same frequency as the amplitude changes observed in the CM. There was no variation in distortion amplitude in the CM and no modulation of auditory nerve discharges when primaries were frequency modulated coherently. It is suggested that amplitude modulation of distortion gives the auditory system its demonstrated sensitivity to minor departures from coherence of frequency-modulated, harmonically-related tones.

Acoustic Stimulation

Contributions of the middle ear to the development of function in the cochlea.

The contribution of middle ear immaturities to the development of cochlear microphonic potential (CM) responses was studied throughout the ontogeny of auditory function in the Mongolian gerbil. CM produced by direct mechanical stimulation of the stapes was compared with CM generated by acoustic stimulation of the intact ear at various postnatal ages. The results indicated that during development acoustically generated CM reflects middle ear as well as inner ear maturational factors. With direct stapes driving, CM was first elicited at 10 days after birth (DAB), two days earlier than with acoustic stimulation. Controlling for the contributions of middle ear immaturity, maturation of the inner ear accounted for approximately a 75 dB improvement in CM thresholds between 10 and 18 DAB. Comparisons between the results obtained with the acoustic and stapes driving stimulation protocols suggested that the major maturational changes in the middle ear conduction apparatus occurred between 14 and 16 DAB. This period was associated with the final stages of resorption of middle ear mesenchyme and ossicular ossification. Before 16 DAB, acoustically evoked CM thresholds reflect approximately a 25 dB loss in sensitivity due to middle ear immaturity.

Acoustic Stimulation

Detuning of cochlear action potential tuning curves at high sound pressure levels: influence of temporal, spectral and intensity variables.

Action potential (AP) tuning curves (TCs), generated by probe stimuli of 60-65 dB SPL with short rise and decay (r&d) times, are less sensitive (have elevated tip thresholds) and are detuned (the frequency is shifted away from that of the probe stimulus, towards a middle frequency of the audiogram). These effects are more pronounced with forward than with simultaneous masking. TCs generated by masking tonal and narrow band noise stimuli are nearly identical, even though the spectrum is much wider for the noise stimulus. Decreasing r&d time has the same effect on TCs generated from both noise and tonal stimuli, even when it only measurably increases the acoustic splatter of the latter. Detuning appears to be related to a temporal-intensity interaction.

Action Potentials

Comparative actions of quisqualate and N-methyl-D-aspartate, excitatory amino acid agonists, on guinea-pig cochlear potentials.

We examined dose-dependent changes in the amplitude of guinea-pig cochlear microphonic potentials (CM), summating potentials (SP) and compound auditory nerve action potentials (CAP) produced after perfusing perilymphatic scalae with artificial perilymph containing either the transmitter candidate, L-glutamate; one of the excitatory amino acid agonists, quisqualate, kainate, N-methyl-D-aspartate (NMDA) or D-glutamate; or the control, alpha-ketoglutarate. None of these compounds significantly altered CM or SP. Kainate abolished CAP, but only partial suppression occurred using maximal effective doses of quisqualate (67%) or L-glutamate (82%). The remaining compounds had only marginal effects on CAP. The potency of quisqualate (EC50 = 14.8 microM) exceeded that of both kainate (EC50 = 66.9 microM) and L-glutamate (EC50 = 1.41 mM). These data suggest the presence of neuronal, possibly postsynaptic, excitatory amino acid receptor subpopulations which are preferentially sensitive to quisqualate and to kainate, but not to NMDA. These findings are discussed in the framework of our hypothesis that the proposed quisqualate and kainate receptors are normally activated by an endogenous excitatory amino acid such as L-glutamate which the hair cells release as a neurotransmitter.

Action Potentials

Transtympanic electrocochleography in patients with syphilis and hearing loss.

Transtympanic electrocochleography was carried out on 18 syphilitic patients (30 ears were tested) most of whom were suffering from the late onset congenital form of the disease. A diphasic action potential with a large negative summating potential on the descending limb was found in 77.7% of ears; the cochlear microphonic potential was always of small amplitude. While these findings are not pathognomonic of syphilis, they are characteristic and may be explained on pathological grounds.

Action Potentials

Identification and separation of acoustic frequency following responses (FFRS) in man.

Frequency following responses (FFRs) to monaural tone bursts were recorded in normal and hearing impaired subjects as the potential difference between an ipsilateral earlobe electrode and a scalp vertex electrode. Whenn the rubber tube coupler between the earphone and the subject's ear was clamped, a stimulus artefact FFR was occasionally recorded. The "biological" FFR had a latency of about 1 msec and an irregular wave form which was made more sinusoidal by the addition of white noise. When the responses to tone bursts of opposite onset phases were added together, a "double frequency" FFR was obtained which had a latency of about 6 msec and whose amplitude was appreciably reduced by white noise. In some hearing impaired subjects (with no neural responses to clicks), this longer latency double frequency component could not be recorded, while in those cases in which the cochlear microphonic potential could be recorded, the shorter latency FFR was also present. It is concluded that the FFR in normally hearing subjects is made up of a short latency cochlear microphonic component and a longer latency neural component.

Adolescent

Usher's syndrome: electrophysiological tests of the visual and auditory systems.

The symptoms of Usher's syndrome - congenital hearing impairment and tapetoretinal dystrophy - are difficult to detect in young children. The electroretinogram (ERG), visual evoked potential (VEP), auditory nerve and brain-stem responses as well as the cochlear microphonic potentials were used to evaluate the defects of the visual and auditory systems in 20 patients, 3-45 years of age. This study demonstrates the usefulness, reliability and convenience of the electrophysiological tests for early diagnosis and functional evaluation of Usher's syndrome.

Adolescent

Bioelectric phenomena in the ototoxicity of nitrogen mustard.

The effects of nitrogen mustard on the electrical potentials of the inner ear were studied, and the results were correlated with the histopathologic findings which have been reported in nitrogen mustard ototoxicity. The endocochlear DC potential (EP) decreased rapidly after an injection of nitrogen mustard (NM). The amplitude of the cochlear microphonics potential (CM) diminished rapidly, and no substantial recoveries were observed. No significant changes in the magnitude of the negative potential of organ of Corti (NPOC) were observed. A large negative summating potential (SP) was recorded even when the amplitude of the CM had diminished.

Acoustic Stimulation