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M C Liberman

Publications and source records attributed to M C Liberman.

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Single-neuron labeling and chronic cochlear pathology. I. Threshold shift and characteristic-frequency shift.

Iontophoretic injections of horseradish peroxidase were used to label single auditory-nerve fibers in cats with permanent, noise-induced or drug-induced threshold shifts. Using these labeling techniques, it was possible to estimate the degree to which the characteristic frequency (CF) of a neuron shifts as its threshold shifts in cases of chronic cochlear pathology. The original CF of an abnormal neuron was estimated by measuring the location of its peripheral terminal along the cochlear spiral and comparing that to data from normal animals on the relation between CF and cochlear location [12]. Data from 25 labeled neurons with estimated threshold shifts varying from 0 to 70 dB suggest that, at least for units with original CF above 1 kHz, the measured CF shifts down as the threshold rises. The largest CF shifts (0.26 to 0.66 octave) were seen in units contacting inner hair cells within 1 mm of cochlear regions in which the entire organ of Corti (including supporting cells) was destroyed. For the abnormal units located more than 1 mm from such regions, the discrepancy between the CF predicted on the basis of fiber location and the CF measured from the tuning curve was less than 0.18 octave even though threshold shifts were comparable in the two groups. Units with the largest CF shifts showed abnormally low slopes on the portion of the tuning curve immediately above CF. This observation suggested a means of identifying abnormal units with significant CF shifts by simple inspection of the tuning curve. The possibility that the degree, and even the direction, of the CF shift varies from high- to low-CF units is discussed.

Animals↗

Single-neuron labeling and chronic cochlear pathology. II. Stereocilia damage and alterations of spontaneous discharge rates.

The spontaneous discharge rates (SRs) sampled from auditory-nerve fibers in cases of chronic cochlear pathology are often abnormally low [17]. The application of intracellular labeling techniques to noise-exposed ears makes it possible to accurately correlate fiber populations showing SR abnormalities with the cochlear locations from which these responses originate. The correlations reveal that a decrease in the mean rates of spontaneous discharge is typically associated with selective loss of the tallest row of stereocilia from the inner hair cells. In cochlear regions where virtually all of the tall stereocilia are missing from the inner hair cells, the maximum rates of spontaneous discharge are less than 1/3 normal values. We suggest that the loss of tall stereocilia causes the decrease in SR because much of the resting current in the inner hair cell normally flows through the stereocilia membrane. Thus, the loss of that membrane leads to a hyperpolarization of the inner hair cell which, in turn, decreases the spontaneous release of vesicles at the synapse. An interpretation is also suggested for the "compression" of the SR distribution commonly seen among high-frequency neurons in normal animals [9].

Animals↗

Single-neuron labeling and chronic cochlear pathology. III. Stereocilia damage and alterations of threshold tuning curves.

Tuning curves were obtained from 100 to 150 auditory-nerve fibers spanning the range of characteristic frequencies (CFs) in each of eight cases of permanent noise-induced and three cases of permanent kanamycin-induced threshold shift. In each ear, from one to six neurons were intracellularly labeled with horseradish peroxidase. Locating the labeled terminals in plastic-embedded surface preparations of the cochlea enabled us to accurately correlate particular tuning-curve abnormalities with the condition of the sensory cells generating them. The correlations between structural and functional changes suggest that a normal tuning-curve tip requires that the stereocilia on both the IHCs and OHCs (especially those from the first row) be normal. Selective damage to the OHCs is associated with elevation of the tips and hypersensitivity of the tuning-curve tails. This tuning-curve pattern also originates from cochlear regions at the basal border of hair cell lesions where the local hair cells (and their stereocilia) appear completely normal at the light-microscopic level. Total destruction of the OHCs in a region in which the IHCs appear normal (as can happen in cases of kanamycin poisoning) is associated with bowl-shaped tuning curves which appear to lack a tip. Combined damage to the IHCs and OHCs (as typically happens in cases of acoustic trauma) is invariably associated with elevation of both tips and tails on the tuning curve. A framework for the interpretation of the results is suggested in which the activity of the OHCs is transmitted via the tectorial membrane to the tall row of stereocilia on the IHCs.

Animals↗

Single-neuron labeling and chronic cochlear pathology. IV. Stereocilia damage and alterations in rate- and phase-level functions.

The rate and phase of auditory-nerve response to tone bursts were studied as a function of stimulus level in normal and acoustically traumatized animals. The rate- and phase-level functions of normal auditory-nerve fibers are often separable into a low-intensity component (component I) and high-intensity component (component II), as defined by a dip in the rate function and a simultaneous abrupt shift in the phase function at stimulus levels near 90 dB SPL [10,12,9]. Baseline data are established by defining the relation between stimulus frequency and the characteristic frequency and spontaneous discharge rate of a fiber normally required for the appearance of these two components in the response. Abnormalities of the level functions are shown to occur in acoustically traumatized ears. Noise-induced threshold shift is often characterized by selective attenuation of component I. In some instances, it appears that component I has been eliminated, leaving a response which is identical in threshold, phase and maximum discharge rate to a normal component II. Results of single-unit labeling in such a case suggest that the selective attenuation of component I is associated with selective loss of the tallest row of stereocilia on the inner hair cells (IHCs). It is suggested that component I is normally generated through an interaction between the outer hair cells and the tall row of IHC stereocilia, while component II requires only the shorter row of IHC stereocilia.

Animals↗

Hair-cell innervation by spiral ganglion cells in adult cats.

A horseradish peroxidase technique was used to trace the peripheral terminations of two types of ganglion cells in adult cats. It was found that large, usually bipolar ganglion cells end on inner hair cells and small, usually pseudomonopolar ganglion cells end on outer hair cells. Thus, a virtually complete segregation of afferent neural inputs from the two types of hair cells was directly confirmed.

Animals↗

Single-neuron labeling in the cat auditory nerve.

Single auditory nerve fibers in the cat were labeled intracellularly with horseradish peroxidase. The sample of fibers was selected to represent different response types over a wide range of characteristic frequencies. All 56 labeled neurons were found to be radial fibers innervating inner hair cells, suggesting that none of the single-unit data reported to date has been from the outer hair cell innervation. Differences in rates of spontaneous discharge and thresholds to tones among these labeled neurons were closely correlated with morphological differences in the caliber and location of their unmyelinated terminals on the body of the inner hair cell.

Animals↗

The cochlear frequency map for the cat: labeling auditory-nerve fibers of known characteristic frequency.

Iontophoresis of horseradish peroxidase was used to label single auditory nerve fibers after determination of threshold tuning curves and rates of spontaneous discharge. The relation between characteristic frequency (CF) and cochlear longitudinal location is reconstructed from 52 labeled neurons in 16 cochleas. The length of the organ of Corti allotted to an octave of stimulus frequency increases steadily from low to high frequencies. Thus there is not a simple linear-distance-to-log frequency conversion. When comparing cochleas of different total length, the best predictor of CF at a given location is the distance from base or apex expressed as a percentage of the total length. The cochlear frequency map derived from these single-neuron labeling experiments is compared to maps derived by a number of different physiological and psychophysical techniques, and the significance of the similarities and differences is discussed.

Action Potentials↗

Morphological differences among radial afferent fibers in the cat cochlea: an electron-microscopic study of serial sections.

The entire unmyelinated portions of 104 radial afferent fibers were reconstructed from serial ultrathin sections through the organ of Corti. Each radial fiber was unbranched and formed a single synapse with one inner hair cell. Fibers innervating the side of the hair cell facing the pillar cells were, in general, larger in diameter and richer in mitochondria than fibers innervating the side of the hair cell facing the modiolus. Some of the thin, mitochondrion-poor fibers had a more complex synaptic junction with the inner hair cell. A fiber classification scheme is suggested which may correlate with the classification of single auditory nerve units according to threshold and rate of spontaneous discharge [5].

Animals↗

Hair cell condition and auditory nerve response in normal and noise-damaged cochleas.

Histological and physiological data are presented from cats born and raised in a low-noise environment and from cats with long-standing, noise-induced threshold shifts. Even after a 1 1/2-year survival from acoustic trauma, there were threshold elevations of roughly 40 dB in the response of single auditory-nerve fibers which could not be correlated with significant loss of hair cells. An attempt was made to correlate these threshold differences with differences in the condition of the sensory cells as seen in a light-microscopic examination of epon-embedded surface preparations. Of all the histological features evaluated, the orderlines of the stereocilia, on both inner and outer hair cells, showed the closest correlation with single-unit thresholds. In the final analysis, most of threshold shift in the noise-exposed ears could be accounted for by loss or damage to sensory cells clearly visible under the light microscope.

Animals↗

Auditory-nerve response from cats raised in a low-noise chamber.

A litter of four cats, born and raised in a soundproofed chamber, was studied in an attempt to determine which, if any, features of the auditory-nerve response from routinely available cats might be due to the chronic effects of noise exposure. Two features of routine-normal response were especially suspect in this regard: (1) a "notch" in the distribution of single-unit thresholds centered at characteristic frequencies (CF's) near 3 kHz and (2) a compression of the distribution of rates of spontaneous discharge for units with CF above 10 kHz. A third feature of response in routine animals was the presence of a small number (roughly 10%) of units with virtually no spontaneous discharge and very high thresholds, sometimes 80 dB less sensitive than high-spontaneous units of similar CF. In the data from chamber-raised animals, the high-spontaneous units showed exceptionally low thresholds at all CF regions, however, there were signs of the midfrequency notch in the threshold distribution of at least two of these animals. The compression of the spontaneous rate distribution was not seen in any of the three most sensitive animals. The data suggest that there is a significant amount of "normal pathology" in the high-CF units from routine animals. Low-spontaneous, high-threshold units were present in all four chamber-raised ears with the same characteristics as in routine animals (exceptionally narrow tuning curves and exceptionally low maximum discharge rates) and at roughly the same percentage of the unit sample. A class of units with medium spontaneous rates and intermediate thresholds could also be identified. The possible significance of a classification of auditory-nerve units according to spontaneous rate is discussed.

Acoustic Stimulation↗

Feedback control of the auditory periphery: anti-masking effects of middle ear muscles vs. olivocochlear efferents.

Both MEM and MOC systems are sound-evoked reflexes to the auditory periphery which can be elicited by sound in either ear. Both MEM and MOC systems can increase thresholds in the auditory periphery: the MEM system acts by stiffening the ossicular chain, the MOC system by decreasing outer hair cell amplification of sound-induced motion in the inner ear. MEM-induced attenuations are largest for low frequency stimuli, MOC-induced attenuations are largest for mid- to high-frequency sounds. Both MEM and MOC systems can have anti-masking effects. The MEM reflex can decrease the masking of high-frequency signals by low-frequency noise (i.e., the upward spread of masking). The MOC reflex is complementary in that it minimizes masking of high-frequency transient signals by high-frequency continuous noise. MEM anti-masking arises by reducing suppressive masking and can improve masked thresholds at high frequencies. MOC anti-masking arises by counteracting excitatory masking. It does not improve masked thresholds, but can improve the detectability of small suprathreshold intensity increments. Anti-masking effects of both MEM and MOC systems should be reduced in cases of sensorineural hearing loss.

Animals↗

Auditory-nerve activity in cats exposed to ototoxic drugs and high-intensity sounds.

The response characteristics of auditory-nerve fibers in normal cats are compared with those in cats exposed to kanamycin and high-intensity sounds. The pathophysiology is characterized by an elevation of the tuning-curve "tips," which is sometimes associated with hypersensitivity of the "tails". Plots of unit thresholds are correlated with patterns of sensory-cell losses in the cochlea. There can be significant shifts in unit threshold without significant loss of hair cells; however, significant hair cell loss is always accompanied by highly abnormal unit thresholds. The presence of inner hair cells seems to be essential for the long-term survival of spiral ganglion cells. An incidental observation is that in the "normal" animal there is almost always a prominent "notch" at 3-4 kHz in the plots of threshold at characteristic frequency, which may have been produced by environmental noise.

Animals↗

Click-evoked gross potentials and single-unit thresholds in acoustically traumatized cats.

Click-evoked gross potentials were recorded from the round windows of 29 cats previously exposed to high-level sounds. The latency and amplitude of the gross neural components of these responses were determined and compared with the patterns of threshold shift measured in single auditory nerve fibers from the same 29 animals. Both of these electrophysiological measures were compared with the patterns of hair cell loss as seen in celloidin sections through the temporal bone. The correlations between single-unit abnormalities and cochlear pathology in these cases have been documented elsewhere. In this report, the correlations between gross-potential abnormalities and cochlear pathology are examined. The diagnostic potential of these correlations is discussed.

Acoustic Stimulation↗