Brian M. Johnstone

Measurement of basilar membrane motion in the guinea pig using the Mössbauer technique

Basilar membrane motion was measured at the 16-19 kHz place of the guinea pig cochlea using the Mössbauer technique. The threshold of the gross cochlear action potential (CAP) evoked by pure-tone bursts was used as an indication of neural threshold. CAP threshold deteriorated progressively after the cochlea was opened and the Mössbauer source placed on the basilar membrane. A close relationship was found between the amplitude of basilar membrane motion at the source place frequency and CAP threshold. Basilar membrane velocity at CAP threshold SPL was about 0.04 mm/s over a 60-dB range of CAP threshold. Intensity functions for basilar membrane motion were linear for frequencies more than an octave below the source place frequency but demonstrated progressive saturation for frequencies greater than an octave below the CF. This nonlinear behavior was eliminated as the CAP threshold became less sensitive and was absent post mortem. Isovelocity curves at the 0.04 mm/s criterion were remarkably similar to frequency threshold curves from primary afferent fibers innervating a similar place on the basilar membrane. The isovelocity curve was a better fit than the isoamplitude curve suggesting that inner hair cells respond to basilar membrane velocity. As the CAP threshold deteriorated, the isovelocit curves lost sensitivity around the best frequency, whereas sensitivity to frequencies below 10 kHz remained constant even after the animal was killed. We suggested that most of the frequency response and nonlinear behavior of inner hair cells and afferent fibers may be found in basilar motion.

Basilar membrane measurements and the travelling wave.

From the original measurements of G. von Békésy (1942) until a few years ago, the basilar membrane was considered to undergo simple passive linear vibration. Recent measurements have completely altered this notion. It is now known that the BM is highly non linear and very sharply tuned. Indeed, BM can now account for most of the properties of the eighth nerve response to sound. The non linearity can be approximated by a hyperbolic function and appears to be part of an active process in the outer hair cell. At the characteristic frequency, CAP threshold (10 dB SPL) corresponds to 0.3 nm motion and the non linearity shows half saturation at 10 nm. The sigmoid shape of the full range BM input-output curve is due to the combination of a less sensitive linear passive component with the added sensitivity of the active non linear function. A hyperbolic input-output function is also present in the cochlear microphonics, and at low frequencies the half saturation value again corresponds to 10 nm BM displacement. With induced threshold loss (e.g. noise trauma) the nonlinearity disappears from the BM, but is still present in the CM. This suggests that the pathology is in the active mechanical feedback process, rather than in the receptor system. It appears that BM mechanics at low amplitudes near the resonant frequency is controlled by a nonlinear mechano-electrical transducer followed by a vulnerable, linear, active mechanism (electro-mechanical?) feeding back in positive phase onto BM vibration.

Outer hair cell receptor current and sensorineural hearing loss

It is argued in this paper that many nonlinear phenomena in audition and many types of sensorineural hearing loss can be explained by a disruption of the mechano-electrical transduction process at the apex of the outer hair cells. This is done using experimental data and a simple model of the active role of outer hair cells in cochlear mechanics based on our previous experiments with acoustic trauma. The causes of sensorineural loss addressed include acoustic trauma, aminoglycoside ototoxicity, intoxication with loop diuretics, hypoxia and Menieres disease. The nonlinear phenomena discussed include loudness compression, two-tone suppression and modulation of cochlear sensitivity by very low-frequency tones. In every case considered the reduction in neural sensitivity was related to the reduction in outer hair cell receptor current in a quantitatively similar way. We conclude that the link is causal.

Kainic acid selectively alters auditory dendrites connected with cochlear inner hair cells

Cochleas of adult guinea pigs and rats, and 6-day-old rat pups, were injected, through the round window, with 2 microliters of artificial classical Konishi perilymph containing 1 nmol kainic acid (KA). 5 min later, they were fixed, removed, and processed for electron microscopy. In all KA-treated cochleas, the injection resulted in a severe swelling of auditory dendrites below the inner hair cells (IHCs). Below the outer hair cells (OHCs), the swelling appeared only in the 6-day-old rats, not in adult animals. These results are significant in three different ways: (1) They confirm the strong difference between afferents innervating the IHCs and the OHCs in adult cochleas. (2) They shed some light on the synaptic plasticity found at the OHC level during synaptogenesis. (3) They support the hypothesis that glutamate, or a related substance, is the IHC neurotransmitter.

Cochlear action potential threshold and single unit thresholds.

There is a close correlation between the sound pressure of tone burst required to affect a primary auditory neuron at its characteristic frequency and that which will produce a detectable N1 response at the same frequency. Units with thresholds from 80--0 db SPL (recorded from damaged and undamaged cochleas) were 0--20 dB , respectively, more sensitive than the action potential response.

The origin of the low-frequency microphonic in the first cochlear turn of guinea-pig

Low-frequency microphonic potentials (100 Hz to 2000 Hz) have been measured in the first turn of the guinea pig cochlea before and after a variety of manipulations of the cochlea. These included ablation of the apical turns, iontophoresis of streptomycin, dc current injection into the first turn, acoustic trauma and two-tone interference with pure tones. These manipulations indicate that the low-frequency microphonic measured in the first turn and at the round window is generated predominantly by the hair cells of this region. It is a convenient and relatively uncomplicated indicator of the integrity of the mechano-electrical transduction process of these cells.

The ototoxic mechanism of cisplatin

The ototoxic mechanism of cisplatin was investigated. Potentiation of cisplatin ototoxicity by furosemide and amino-oxyacetic acid (AOAA) was observed. Substantial hearing loss in cisplatin-deafened animals was accompanied by normal values of the endocochlear potential and a reduction in the sensitivity of the 2f1-f2 distortion products. The loss in dB of the sensitivity of the distortion products correlated extremely well with the loss of the neural sensitivity in dB. There was also a relationship between the fractional reduction of the low frequency (1000 Hz) microphonic potential and hearing loss in dB. Iontophoresis of cisplatin into scala media resulting in the immediate loss of neural thresholds at the site of iontophoresis. It is concluded that cisplatin caused the hearing loss by blocking OHC transduction channels.

Temporary threshold shift modified by binaural acoustic stimulation

Monaural losses in hearing sensitivity induced by an intense pure tone could be reduced if an acoustic stimulus of the same frequency was simultaneously delivered to the other ear. The reduction was eliminated when the contralateral stimulus was set at a frequency other than the ipsilateral trauma frequency and also after the administration of strychnine, a known blocker of auditory efferent activity. This suggests that acoustic activation of auditory efferents is responsible for the reduced ipsilateral sensitivity loss.

Stimulus‐related potassium changes in the organ of Corti of guinea‐pig.

1. Potassium concentration was measured with double‐barrelled K+‐selective microelectrodes within the organ of Corti in the first turn of the guinea‐pig cochlea. 2. Penetration of the electrode from scala tympani through the basilar membrane was accompanied by an increase in K+ resting level from 3.0 mmol/l in perilymph to 3.4 mmol/l in cortilymph (n = 8). K+ resting level was not significantly different in various extracellular regions of the organ of Corti. On penetration of the cuticular plate, the K+ level reached 140 mmol/l simultaneously with the occurrence of a +80 mV endocochlear potential. Impalement of hair cells and supporting cells was accompanied by an increase in K+ level, but intracellular K+ level was not systematically measured. 3. Stimulation with pure tones over the frequency range 500 Hz to 25 kHz produced changes in the K+ level in the organ of Corti. The magnitude of these changes was dependent on stimulus frequency and intensity. At high sound intensities the K+ level in the tunnel of Corti could increase by typically 1 mmol/l, while a maximum increase of 3 mmol/l with respect to the resting level was observed immediately adjacent to inner hair cells. 4. During brief exposures to moderate intensity, pure tone acoustic stimulation (10 s, less than 80 dB SPL (sound pressure level] of frequency 4 kHz or greater the K+ level in the extracellular fluid of the organ of Corti rose monotonically to a steady peak level. On cessation of the stimulus the K+ level fell monotonically with a time constant of about 2 s to a level close to the pre‐stimulus level. In some cases this level was slightly above the pre‐stimulus level. 5. For brief exposures to moderate intensity sound (10 s, less than 80 dB SPL) the extracellular potential in the organ of Corti became more positive. The amplitude of this sound‐evoked change adapted during stimulation to a level approximately one‐fifth of its initial value. Upon cessation of the stimulus the potential fell transiently below its pre‐stimulus level, before recovering to that level. The time constant of these changes was between 2 and 3 s. 6. Iso‐response tuning curves for the sound‐evoked elevation in K+ level in the organ of Corti in animals in good condition were similar to iso‐rate tuning curves for primary afferent fibres reported previously.(ABSTRACT TRUNCATED AT 400 WORDS)

Acoustic trauma in the guinea pig cochlea: Early changes in ultrastructure and neural threshold

Scanning microscopy was used to examine guinea pig cochleas for structural damage immediately after exposure to a pure tone ranging from 96 to 129 dB SPL. Functional changes to the cochlear neural sensitivity were assessed using the N1 audiogram. principal findings were: (1) The order of damage to receptor cells with increasing sound intensity was OHC1, then IHC, then OHC2 and OHC3. (2) The spatial distribution of damage to OHC1 and IHC differed with IHC tending to show damage mainly in the vicinity of the exposure frequently location and OHC1 damage spreading basal-ward of this point. (3) N1 threshold losses spread progressively to lower frequencies as exposure intensity increased. This was accompanied by an apical spread of damage to the receptor cells.