Ac Cochlear Potential Research Articles

Using the Cochlear Microphonic as a Tool to Evaluate Cochlear Function in Mouse Models of Hearing

The cochlear microphonic (CM) can be a useful analytical tool, but many investigators may not be fully familiar with its unique properties to interpret it accurately in mouse models of hearing. The purpose of this report is to develop a model for generation of the CM in wild-type (WT) and prestin knockout mice. Data and modeling results indicate that in the majority of cases, the CM is a passive response, and in the absence of outer hair cell (OHC) damage, mice lacking amplification are expected to generate WT levels of CM for inputs less than approximately 30 kHz. Hence, this cochlear potential is not a useful metric to estimate changes in amplifier gain. This modeling analysis may explain much of the paradoxical data in the literature. For example, various manipulations, including the application of salicylate and activation of the crossed olivocochlear bundle, reduce the compound action potential but increase or do not change the CM. Based on this current evaluation, CM measurements are consistent with early descriptions where this AC cochlear potential is dominated by basal OHCs, when recorded at the round window.

Link between functional and morphological changes in the inner ear--functional changes produced by ototoxic agents and their interactions.

Common potentials used to evaluate cochlear function are the ac cochlear potential (ACCP), N1 and the positive dc endocochlear potential (EP). The ACCP is an electrical analogue of the sound stimulus; its source is the electrical activity of the cochlear hair cells. N1 is a volume conductor recorded action potential of the auditory nerve. The EP is the positive polarization of the middle compartment of the cochlea (scala media) with respect to the other compartments (the scalae tympani and vestibuli); the stria vascularis is apparently responsible for the EP. Generally, ototoxic drugs and very intense broad-band noise affect the basal portion of the cochlea first and, because of tonotopic organization, the ACCP responses to high frequency pure tones are affected before those to the low frequencies. However, the correlation between the effect of an ototraumatic agent on the ACCP and its effect on cochlear morphology is not always reliable. The correlations between changes in N1 and EP and in cochlear morphology are even less precise. Also discussed will be the cochlear effects of noise and the ototoxic interactions between drug/drug, noise/drug, and noise/drug/otitis media.

Abolition of the negative endocochlear potential as a consequence of the gentamicin—furosemide interaction

The DC endocochlear potential and the AC cochlear potential in response to a 4 kHz tone were recorded in pigmented guinea pigs before and during ototoxic damage induced by sequential administration of the aminoglycoside antibiotic, gentamicin, and the loop diuretic, furosemide. Within 4 h significant diminution of the amplitude of the AC cochlear potential was accompanied by an almost complete abolition of the negative diffusion potential revealed by either furosemide administration or terminal anoxia. Thus, one of the effects of this interaction appears to involve a reduction in the potassium permeability of the cochlear partitions.

Quantitative Relationships of the Ototoxic Interaction of Kanamycin and Ethacrynic Acid

We determined the range of doses of kanamycin sulfate and ethacrynic acid that results in an ototoxic interaction in guinea pigs. In addition, we determined the time interval between the administration of the two drugs that is needed to produce this interaction. In all cases, the magnitude of the ototoxic lesion was determined by measuring the cochlea's ability to generate both the sensitivity and intensity functions of the ac cochlear potential. In addition, the cochlear pathologic conditions, as determined by counting the number of missing hair cells in the organ of Corti, was found to correlate highly with the ac cochlear potential data. The dosage range of ethacrynic acid during which the interaction occurs is very narrow, while the dose range of kanamycin is very large.

AC cochlear potentials in an animal model for human atherosclerosis: Relationships to blood pressure, vascular disease, and blood coagulation

We have discovered an animal model, the white carneau pigeon, which for the first time, through its use in laboratory experiments, has demonstrated significant correlations between the magnitude of inner ear electric potentials and standard measures of blood pressure, blood cholesterol, and blood coagulation. Also, we have found that a new blood coagulation research tool—the sonoclot machine—can demonstrate blood coagulation physiology parameters which correlate highly with cochlear potentials in our animal model. The above results will be discussed in relation to our previous findings of relationships of atherosclerosis to hearing in the same animal model. [Work supported by NIH Grant Number NS‐12013.]

Comparative Ototoxic Liability of Netilmicin and Gentamicin

Netilmicin sulfate is a new aminoglycoside antibiotic currently undergoing clinical investigation. All of the aminoglycoside antibiotics now in clinical use are ototoxic. This study was done to determine the ototoxic liability of netilmicin when it is compared directly with gentamicin sulfate. Groups of ten guinea pigs each were given doses of 0, 50, 100, or 150 mg/kg of either gentamicin or netilmicin daily for four weeks. After a two-week stabilization period, the Preyer pinna reflex, the cochlea's ability to generate the ac cochlear potential, and the missing hair cells from the cochleas were determined. Additionally, the pharmacokinetics of both drugs in the plasma and perilymph were determined. Little or no cochlear damage was detected with netilmicin, even at the highest dose, while even the smallest dose of gentamicin produced measurable changes in cochlear function.

Combined effects of noise and neomycin. Cochlear changes in the guinea pig.

Cochlear damage resulting from the combination of neomycin with acoustic overstimulation was investigated in guinea pigs. Four groups of animals received subcutaneous injections and exposure to broad band noise daily for 7 days, as follows: I. Neomycin (200 mg/kg) followed by 10 hours of noise at 115 dB SPL; II. Saline followed by 115 dB noise: III. Neomycin followed by low intensity noise (45 dB as an acoustic control); or IV. Saline followed by 45 dB noise. After a 30 day stabilization period, each ear was examined electrophysiologically and histologically. Measures of cochlear integrity included AC cochlear potentials from 100 Hz through 20 kHz as well as outer hair cell (OHC) counts. A marked interaction leading to augmentation of damage was found when neomycin was combined with 115 dB noise (Group I). Losses in cochlear sensitivity, averaged across all frequencies, amounted to 62 dB in Group I, whereas the averaged losses for Groups II and III were only 16 dB and 17 dB respectively. Loss of OHC's was close to 100% in Group I, while OHC losses were only 17% in Group II and 26% in Group III.

Histopathologic correlates of otoneurologic manifestations following head trauma.

The clinical course of patients dying of head trauma and the physiologic evaluation of audition in guinea pigs subjected to several forms of head trauma are correlated with the histopathologic findings in the brains and temporal bones. In the patients there was wide spread hemorrhage, edema, disorganization and disruption of neural tissue. Loss of Purkinje cells and other neural elements was prominent. The temporal bone findings in the patients included laceration of and hemorrhage into the VIIIth nerve as well as bleeding into the scala tympani. The membranous labyrinths demonstrated no specific changes secondary to the trauma. The guinea pigs developed a central form of hearing loss with elevated thresholds for evoked responses from the inferior colliculus and normal AC cochlear potentials. In the animals hemorrhage in the substance of the brain, necrosis of neural tissue, edema, disorganization and disruption were prominent. Although there was extravasation of blood in the tympanic and vestibular scalae, the membranous structures of the inner ears were well preserved.

Interaction between Agents Which Produce Temporary Hearing Threshold Shifts: Intense Sound and Sodium Salicylate

In previously reported experiments we have shown that an intense sound exposure can temporarily depress the cochlear nerve evoked potential (N1) while not affecting the alternating current cochlear potential [J. Acoust. Soc. Am. S3, 326 (1973)]. Sodium salicylate was likewise found to produce a temporary effect on N1 only. In this experiment it was found that when these agents are given together they produced a greater change in N1 than either agent alone, but not more than would be expected from a simple summation. This combined effect- of both agents on N1-was also temporary. The interaction of these agents did not affect the ac cochlear potential. This interaction—of intense sound and sodium salicylate-does not produce the permanent damaging interaction effects reported for other ototoxic drugs.

Future Implications for Implantable Hearing Aids

The procedure for testing implantable-type hearing aids has been developed so as to utilize laboratory animals as well as the human. In the case of laboratory animals the test consists of measuring the ac cochlear potentials of the inner ear when that ear is activated by the implantable hearing aid. In the same manner distortion production is evaluated. The same procedure has been utilized to produce tapes of speech discrimination material when the animal in question had known damage to its inner ear. The speech discrimination tapes were recorded when the ear was activated by the best possible acoustical drives and also when the ear was activated by the implantable hearing aid. These tapes were then used to test the speech discrimination ability of young normal hearing adults. The implantable device produced 16% better speech discrimination. The speech discrimination ability of sensory neural impaired adults were tested using both acoustic and the implantable aid deliveries. The possible advantages of the implantable hearing aid are: (1) absence of ringing feedback; (2) possibility of improved speech discrimination in competing background noise; (3) and improved efficiency of delivery.

Evidence for a Possible Genetic Influence on Noise-Induced Cochlear Damage

Two strains of guinea pigs were exposed to a 1-kHz tone at +50 dB re 1 dyn/cm2 for 30 minutes. One of these strains was genetically homogeneous, while the other strain was genetically heterogeneous. A 1-µV isopotential curve for the ac cochlear potential was obtained immediately before exposure to the damaging sound, as well as 10 minutes and 56 days after the sound exposure. The isopotential curves obtained from the homogeneous group were significantly less variable than the curves obtained from the heterogeneous group. This difference in variability was more pronounced 10 minutes after the damaging exposure than it was 56 days after the exposure.

Changes in the Auditory Nerve Evoked Potential after Intense Sound Stimulation

Intense sounds were found to produce a decrement in the nerve evoked potential (NEP) at a lower sound pressure level than that which produced a decrement in the ac cochlear potential. Both types of potentials were recorded from the round window of guinea pigs. Guinea pigs were exposed to pure tones of 3, 4, 6, and 12 kHz, at 95–115 dB SPL (5 dB below the maximum cochlear potential output), for 15–30 min. These intensities produced no noticeable effect on the cochlear potential but produced a marked decrement (up to 30 dB) in the NEP. The greatest loss in the NEP wa at 12 oct above the stimulating frequency. These findings correspond to the reported shifts in hearing thresholds.

Effects of Choline Salicylate on the AC Cochlear Potential in Guinea Pigs

AC cochlear potentials were recorded from the round window of guinea pigs anesthetized with Nembutal. Following placement of the electrode, the auditory bulla was closed and pure tones were presented via a speaker located 5 cm from the ear. Intensities were determined with calibrated Brüel & Kjær probe tubes and condenser microphones at the opening of the external auditory meatus. One microvolt contours examined with a General Radio wave analyzer (3-Hz bandwidth) across frequency (0.2 to 20 kHz) were found to agree with accepted guinea pig sensitivity curves. Following oral administration of choline salicylate, a rapid and significant decrease in the AC cochlear potential was observed. Following a peak effect (at 3–4 h) and plateau, initial recovery was noted. The effect was drug dose dependent. The effect was frequency specific, with the greatest influence on the middle-frequency range. The maximum amplitude at the point of nonlinearity of the AC cochlear potential was reduced with drug. Also the point of nonlinearity was reached at a higher intensity of tonal stimulation following drug administration. Detailed findings on the cochlear effects of choline salicylate will be described. The interpretation of these effects on generation of the AC cochlear potential will be discussed. [This research was supported by an NIH grant and by the Deafness Research Foundation.]

Intracochlear Perfusion of Synthetic Perilymph: Controls and Applications

The utilization of cochlear perfusion as a tool for the study of cochlear physiology is not new. Both perilymphatic and endolymphatic perfusions have been done. However in these studies little or no data were given to indicate that the cochleas involved in these experiments were damaged. For our studies a “synthetic perilymph” solution containing the following ingredients (millimoles/liter) was prepared daily just prior to use: NaCl, 136.8; KCL, 5.6; CaCl2, 2.16; NaHCO3, 11.9; MgCl2, 0.491; Na2HPO4, 0.352; glucose, 4.44. The pH of the final solution was 7.95–8.05. For perfusion, glass pipets were inserted into both scala media and scala tympani of the basal turn of the guinea pig cochlea. Perfusion of the perilymphatic space at a speed of 0.1 milliliters/min was continued for 2 min. The ac cochlear potential and/or the N1-evoked potential was monitored from a round-window electrode. In order to check for procedural damage, an electrophysiological assessment of the cochlea was made before and after drilling the cochlea for the insertion of the perfusing pipets, as well as before and after perfusing with the synthetic perilymph. Data on the effect of perfusing solutions containing neomycin, Na salicylate, and Na cyanide will be presented. In addition, the effect of temperature of the perfusing solution on cochlea electrophysiology will be discussed.

Modes of Auditory Response in the Fissiped Carnivores

As part of a program to furnish preliminary but scientifically acceptable estimates of hearing for a broad sample of representative mammals, ac cochlear potentials (CM) were measured in at least one representative from each of the seven fissiped carnivore families. A total of 66 individuals from 12 species were studied. Several response parameters including CM sensitivity level, response bandwidth, and maximum output were used to evaluate peripheral auditory efficiency. It was found that although interspecies differences in performance were great, it was possible to establish common patterns of response. The relation of these groupings to conventional taxonomic classification and to possible artifacts associated with the method of recording will be discussed. [This research was supported by the U. S. Public Health Service under a grant from the National Institute of Neuroogical Diseases and Blindness.]

Exploration of Cochlear Potentials in Guinea Pig with a Microelectrode

The ac (“microphonic”) cochlear potential and the positive dc “endolymphatic” potential have been recorded simultaneously as the exploring electrode was introduced into scala media or as other parameters were varied. Negative intracellular de potentials were demonstrated in the cells of the organ of Corti. The zone of positive endolymphatic potential is bounded by the reticular lamina, not by the basilar membrane. The cochlear microphonic reverses phase as the exploring electrode penetrates the reticular lamina. A dc polarizing current with the positive pole in scala media (and negative in scala tympani) increases the cochlear microphonic just as it does when the positive pole is located in the scala vestibuli. These facts indicate that the source of the ac (microphonic) potential seems clearly to be at the hair-bearing end of the hair cells and that the source of the dc endolymphatic potential is probably here also, while Reissner's membrane is not the source of either the ac or the dc potential. No steady dc current flow outside scala media was found such as would be expected if stria vascularis were the dc source and if the hair cells modulated a dc current flow through them. The dc endolymphatic potential may be increased by as much as 10 percent if and while the basilar membrane is displaced toward scala vestibuli and may be decreased to 50 percent or less when and while it is displaced toward scala tympani. Isotonic solutions rich in potassium depressed the ac potential and nerve responses when introduced into scala tympani but not when in scala vestibuli only. The. dc potential, however, was not altered by high potassium concentration in scala tympani.