Biomedical subjects

M C Liberman

Publications and source records attributed to M C Liberman.

At least 55 records · Page 3Linked to original sources

PubMed1990

Afferent and efferent innervation of the cat cochlea: quantitative analysis with light and electron microscopy.

The purpose of the present study was to describe the longitudinal and radial gradients of cochlear innervation in the cat. To this end, afferent and efferent terminals of both the inner (IHC) and outer hair cell (OHC) regions were reconstructed from serial ultrathin sections at six and eight cochlear locations, respectively, corresponding to roughly octave intervals of characteristic frequency (CF). Analysis of the afferent innervation of the IHCs showed 1) the number of radial fibers per IHC rises from 10 per IHC at the 0.25 kHz region to a maximum of 30 per IHC at the 10 kHz locus; 2) branching of radial fibers is essentially restricted to regions apical to the 1.0 kHz point; and 3) there are significant differences in synaptic-body morphology for synapses on different sides of the IHC, corresponding to known differences in afferent threshold and rate of spontaneous activity. With respect to efferent innervation in the IHC area, we found 1) that there were numerous vesicle-filled terminals contacting every IHC examined; however, those with obvious synaptic specialization were confined to the most apical regions; and 2) there were roughly the same numbers of efferent synapses per radial fiber at all cochlear locations; however, at each location, radial fibers contacting the modiolar side of the hair cell (corresponding to high-threshold afferents) showed significantly more efferent synapses than radial fibers contacting the pillar side. Analysis of the OHC afferent innervation showed 1) a clear rise in numbers of terminals per OHC from roughly 3 per cell in the base to 15 per cell in the apex, 2) no systematic differences in the numbers of terminals as a function of OHC row, and 3) that synaptic bodies at the OHC afferent synapse are common only apical to the 1.0 kHz locus. Counts of efferent terminals on OHCs revealed 1) maximal numbers (9 per OHC) between the 6 and 24 kHz regions and 2) striking decrease in terminal counts from first- to third-row OHCs. Ultrastructural data on efferent innervation were compared quantitatively with light-microscopic analysis of cochleas immunostained (with antibody to synaptophysin) to reveal all vesiculated terminals.

Afferent Pathways↗

PubMed1990

Effects of chronic cochlear de-efferentation on auditory-nerve response.

The olivocochlear bundle was sectioned at the floor of the fourth ventricle in a series of cats. From three to thirty weeks post-operatively, recordings were made from single auditory-nerve fibers. Tuning curves, spontaneous discharge rates, and rate-level functions for tones at the characteristic frequency were measured and compared to normal data. Light- and electron-microscopic analysis of the cochleas suggested the lesions were complete, for both classes of cochlear efferents, in three cases. Electrophysiological data from these cases showed normal thresholds, tuning curves and rate-level functions; however, the distributions of spontaneous activity suggested significant decreases in average rates in the de-efferented cases.

Acetylcholinesterase↗

PubMed1990

Quantitative assessment of inner ear pathology following ototoxic drugs or acoustic trauma.

Techniques currently used in the assessment of structural and/or functional damage to the peripheral auditory system are summarized. Two histological approaches are described: one which allows light microscopic evaluation of all structures of the auditory periphery, and a second which concentrates on the sensory cells and their innervation. The latter technique allows electron microscopic analysis of selected regions after a thorough light microscopic survey. Two electrophysiological methods are described as well: a single-fiber approach which provides detailed information about cochlear condition at all frequency locations and a simpler and faster evoked-potential approach which is well suited to screening for cochlear changes. The correlations between structural and functional changes are described using examples from studies of acoustic injury of the inner ear.

Animals↗

PubMed1989

Effects of contralateral sound on auditory-nerve responses. I. Contributions of cochlear efferents.

The response properties of single auditory-nerve fibers in barbiturate-anaesthetized cats were recorded with and without simultaneous presentation of sound to the contralateral ear. The tendons to the middle ear muscles on both sides were cut before all experiments, and contralateral stimuli were restricted to levels below the threshold for crosstalk to the ipsilateral ear. Contralateral tones and broad-band noise were found to suppress the responses of auditory-nerve afferents to ipsilateral tones at their characteristic frequency (CF), but not to tones off CF. The suppression due to contralateral sound required approximately 100-200 ms to develop and to decay. When the contralateral stimuli were tones at the CF, the strongest suppression was observed in low- and medium-spontaneous-rate units with CFs between 1 and 2 kHz. The suppressive effect of contralateral sound completely disappeared immediately after severing the entire olivocochlear bundle (OCB) within the internal auditory meatus. the completeness of the OCB cuts was assessed histologically. Most of the suppressive effect remained after lesions to the OCB in the floor of the IVth ventricle which eliminated the crossed olivocochlear projection but spared most of the uncrossed projection. It is argued that this suppressive effect of contralateral sound is mediated by the uncrossed olivocochlear efferents to the outer hair cells.

Acoustic Stimulation↗

PubMed1989

Effects of contralateral sound on auditory-nerve responses. II. Dependence on stimulus variables.

The suppression by moderate-level contralateral sound of auditory-nerve-fiber responses to ipsilateral stimuli at the characteristic frequency (CF) was studied in barbiturate-anesthetized cats. The dependence of suppression strength on ipsilateral and contralateral stimulus variables, including level, frequency, bandwidth, and timing relationships, was investigated. The principal findings were: (1) Contralateral-sound suppression is greatest when the ipsilateral stimulus level is within the dynamic range of the unit. (2) When the contralateral stimuli are tones, suppression is greatest when the contralateral tone frequency is at or near CF. (3) Units with CFs above 3-4 kHz are only weakly suppressed by contralateral CF tones but more strongly suppressed by contralateral broad-band noise. (4) Continuous contralateral stimuli are significantly more effective suppressors than are gated stimuli. The characteristics of contralateral-sound suppression are compared with the physiology and anatomy of the uncrossed medial olivocochlear efferents, the subset of efferents which are the primary mediators of the effect.

Acoustic Stimulation↗

PubMed1989

Rapid assessment of sound-evoked olivocochlear feedback: suppression of compound action potentials by contralateral sound.

The compound action potential (CAP) measured at the round window of anesthetized cats in response to low-level tone pips can be significantly suppressed by addition of tones or noise to the opposite ear. This contralateral-sound suppression disappears upon transection of the olivocochlear bundle. The frequency and level dependence of the suppression phenomenon are well explained by known sound-evoked discharge properties of single olivocochlear neurons. Thus, the contralateral-sound suppression of cochlear CAP should prove useful as a rapid measure of the magnitude of the sound-evoked efferent feedback to the cochlea.

Animals↗

PubMed1988

Brainstem branches from olivocochlear axons in cats and rodents.

Horseradish peroxidase was used to label axons of olivocochlear (OC) neurons by intracellular injections in cats and extracellular injections in rodents. These axons arise from cell bodies in the superior olivary complex and project to the cochlea. En route to the cochlea, the thick axons (greater than 0.7 micron diam.) of medial olivocochlear (MOC) neurons formed collaterals that terminated in the ventral cochlear nucleus, the interstitial nucleus of the vestibular nerve (in cats), and the inferior vestibular nucleus (in rodents). The thin axons (less than 0.7 micron diam.), presumed to arise from lateral olivocochlear (LOC) neurons, did not branch near the CN. Within the CN, the MOC collaterals tended to ramify in and near regions with high densities of granule cells, regions also associated with the terminals of type II afferent axons (Brown et al.: J. Comp. Neurol. 278:581-590, '88). These results suggest that those fibers associated peripherally with outer hair cells (MOC efferents and type II afferents) are associated centrally with regions containing granule cells, whereas those fibers associated with inner hair cells peripherally (LOC efferents and type I afferents) are not.

Afferent Pathways↗

PubMed1988

Physiology of cochlear efferent and afferent neurons: direct comparisons in the same animal.

Exposure of the vestibulo-cochlear anastomosis in the cat allows single-unit recording of afferent fibers originating from inner hair cells and olivocochlear efferent fibers to the outer hair cells. Comparison of data obtained from individual animals show similarities in absolute threshold and dynamic range between the efferent fibers and that subset of auditory-nerve afferents with low spontaneous rates and high thresholds [Liberman (1978) J. Acoust. Soc. Am. 63, 442-455]. The afferent-efferent comparisons also show that interanimal variability in efferent excitability (thresholds and maximum discharge rates) is directly correlated with variation in the mean spontaneous discharge rate of the afferent fiber population. It is suggested that interanimal differences in efferent excitability may explain some of the interanimal variability in susceptibility to acoustic trauma.

Animals↗

PubMed1988

Afferent innervation of outer hair cells in adult cats: I. Light microscopic analysis of fibers labeled with horseradish peroxidase.

Outer spiral fibers (OSFs), the afferent innervation of the outer hair cells (OHCs), were retrogradely labeled following horseradish peroxidase injections into the cat's auditory nerve. The peripheral branching patterns of 85 OSFs from adult cochleas were reconstructed. Fibers contacted OHCs via terminal or en passant swellings; however, the latter were seen exclusively in the apical half of the cochlea. Many OSFs also gave off branches ending on structures other than OHCs. Fibers in the cochlear apex were much more highly branched than in the base. Most fibers contacted only one row of OHCs, and more fibers contacted row 1 than row 2 or row 3 OHCs. Third-row fibers were the most highly branched in all cochlear regions. These results are consistent with a growing body of morphological evidence that suggests that the peripheral branching patterns of OSFs may be fundamentally similar in all mammalian ears.

Afferent Pathways↗

PubMed1988

Afferent innervation of outer hair cells in adult cats: II. Electron microscopic analysis of fibers labeled with horseradish peroxidase.

Outer spiral fibers (OSFs) were retrogradely labeled with injections of horseradish peroxidase. After the peripheral arborization patterns were reconstructed at the light microscopic level (Simmons and Liberman, '88), restricted regions of selected fibers were analyzed via electron-microscopic reconstruction of serial sections. The ultrastructural data in the present study suggested that the contact between the outer hair cell (OHC) and the terminal swellings of OSFs corresponds to the afferent synapse described in numerous other ultrastructural studies. The en passant swellings that contacted OHCs also appeared to be points of synaptic contact. However, en passant synapses were not always associated with a swelling of the OSF at the point of contact: thus, the light-microscopic reconstructions probably underestimate the numbers of synapses. OSF branches terminating well below the OHCs were seen to end most commonly in intimate contact with the Deiters' cells. Membrane specialization was occasionally seen at this point of contact; however, the specialization was sufficiently undifferentiated to preclude identification.

Animals↗

PubMed1988

Response properties of cochlear efferent neurons: monaural vs. binaural stimulation and the effects of noise.

1. Discharge properties of olivocochlear efferent neurons were measured in anesthetized cats. Previous studies of these neurons concentrated on monaural stimulation with tones and found sound-evoked discharge rates rarely exceeded 60 spikes/s (16, 20). In the present study, rates as high as 140 spikes/s were achieved by binaural stimulation and/or the addition of noise. Based on studies on the known effects of electrically stimulating the efferents such high rates of sound-evoked efferent activity probably have significant feedback effects on the auditory periphery. 2. Spontaneous discharge rate (SR) was weakly correlated with threshold among efferent neurons: those with SRs greater than 1 spikes/s were generally more sensitive than spontaneously inactive fibers. The discharge rate measured in the absence of acoustic stimulation was shown to be dependent on stimulation history: some units with zero SR became spontaneously active after several minutes of continuous noise stimulation. 3. For stimulation with monaural tones, efferent excitability varied with characteristic frequency (CF): units with CF less than 10 kHz tended to have lower thresholds, higher discharge rates, and shorter latencies than higher CF units. These differences could be minimized by the addition of broadband noise (see below). 4. When tones were presented to one ear at a time, most efferent units appeared monaural (91%), with roughly two-thirds excited by ipsilateral stimuli and one-third by contralateral stimuli. However, the effects of simultaneous stimulation of the two ears suggested that the great majority of efferent units have binaural inputs: the addition of opposite-ear noise or tones, which presented alone were not excitatory, typically enhanced the response to main-ear stimulation. This type of binaural facilitation was strongest among low-CF efferents when the opposite-ear stimuli were tones, and strongest among high-CF units when the opposite-ear stimulus was broadband noise. 5. The binaural facilitation seen using opposite-ear noise both lowered the threshold (by as much as 40 dB) and increased the discharge rate (by as much as 80%) to tones presented in the main ear. Significant facilitation was seen with noise levels as low as 25 dB SPL or tone levels as low as 30 dB SPL. In general, the weaker the response to monaural stimuli, the stronger the binaural facilitation. 6. The facilitatory effects of stimulation with continuous noise could outlast the stimulus. Persistent increases in efferent sensitivity were documented following 10-min exposures to broadband noise at 85-115 dB SPL.

Acoustic Stimulation↗

PubMed1987

Acute ultrastructural changes in acoustic trauma: serial-section reconstruction of stereocilia and cuticular plates.

Single-unit recordings were made from populations of auditory-nerve fibers in 12 cats before and after acoustic overstimulation. Cats were killed 4 to 16 h after exposure, and the cochleas were analyzed at the light- and electron-microscopic levels. The exposures were designed to create 40 to 60 dB of acute threshold shift. Physiological changes were similar to those seen in cases of permanent threshold shift: tuning curves with elevation of 'tips' and 'tails' were associated with significant decreases in the mean spontaneous discharge rates; tuning curves with elevated tips but hypersensitive tails were associated with clear elevation of the mean spontaneous rates. At the light-microscopic level, none of the ears showed any significant stereociliary pathology. Some of the ears showed no light-microscopic pathology whatsoever, while others showed signs of swelling and vacuolization in both inner and outer hair cell areas in cochlear regions appropriate to the CF regions showing threshold shifts. The presence or absence of these light-microscopic changes was, to some extent, dependent on the nature of the exposure stimulus. At the electron-microscopic level, in addition to apparent swelling of radial afferent terminals, the inner hair cells themselves were swollen. In two cochlear regions (from two ears) which showed acute threshold shifts of 20 to 40 dB, but no light-microscopic changes, serial-section ultrastructural analysis of stereocilia and cuticular plates was performed. In contrast to the situation in ears with permanent threshold shifts [(1986) Hear Res. 26, 65-88], there was no pathology in the intracuticular portion of the stereocilia rootlets. There were, however, significant changes in the lengths of the supracuticular portion of the rootlets. It is suggested that this attenuation of the supracuticular rootlet could decrease the stiffness of the stereocilia tufts and thereby change the tuning properties and sensitivity of the cochlear partition.

Animals↗

PubMed1987

Chronic ultrastructural changes in acoustic trauma: serial-section reconstruction of stereocilia and cuticular plates.

Two cochleas with permanent, noise-induced threshold shifts of 40 to 60 dB (as measured by responses of single, auditory-nerve fibers) were analyzed in detail, first at the light-microscopic level, and subsequently with transmission electron microscopy of serial sections. The light-microscopic analysis showed that there was little hair cell loss, but widespread damage to the stereocilia, especially those on the inner hair cells and first-row outer hair cells. Transmission electron microscopy revealed no pathology in any cells or organelles in the organ of Corti except for the stereocilia and their rootlets. Stereocilia tufts on first-row OHCs and IHCs were badly damaged; those on second- and third-row OHCs appeared ultrastructurally normal. Within the IHC tuft, the damage to the tall, outer row of stereocilia was often selective: the shorter rows could remain ultrastructurally normal even when the tall row was completely missing. The data suggested that most of the structures which appear normal in a careful light-microscopic analysis are also normal at the ultrastructural level. This strengthens earlier suggestions that the correlations between light-microscopic stereocilia changes and alterations in single-unit physiology are causal in nature. The most common stereocilia pathologies were fracture, attenuation or complete loss of the stereociliary rootlets, especially in the region of the cuticular plate near the endolymphatic surface of the cell. The degree and extent of these changes were well correlated with the degree and extent of stereocilia disarray. Abnormalities of the actin-filament matrix within the stereocilia were extremely rare in unfused stereocilia, however, they were common when the stereocilia were part of a fusion bundle. Fusion of stereocilia was always associated with ectopic supracuticular cytoplasm. Based on the ultrastructural observations, different sequences of structural changes preceding the generation of disarray, loss or fusion of stereocilia are suggested.

Animals↗

PubMed1986

Physiology and anatomy of single olivocochlear neurons in the cat.

A surgical approach to the cat's VIIIth nerve has been developed which allows recordings to be made from efferent fibers of the olivocochlear bundle (OCB) as well as primary afferent fibers, without compromising the acoustic responsiveness of either ear. The designation of OCB fibers as those with regular interspike intervals was confirmed in five cases by intracellular labeling with horseradish peroxidase. Labeled fibers could be traced centrally to somata in the superior olivary complex and peripherally to large endings on outer hair cells. The locations of the labeled neurons are consistent with a classification as cells of the medial olivocochlear system [Warr and Guinan (1979): Brain Res. 173, 152-155]. Within the cochlea, efferent neurons branched profusely to innervate as many as 84 outer hair cells over as much as 2.8 mm of the organ of Corti. Efferent units had tuning curves which were similar to those of primary afferents, although most were somewhat more broadly-tuned than afferents from the same animal. The cochlear region innervated by an efferent neuron was always close to the place where afferent fibers of the same characteristic frequency (CF) would be found. Most efferents (89%) were excited by only one ear and showed no spontaneous activity. Neurons with an ipsilateral response (n = 3) had cell bodies in the contralateral brainstem and vice versa (n = 2). Binaural units (none of which were labeled) often had spontaneous discharge and were generally restricted to low-CF regions. Differences between low- and high-CF units, which cut across the monaural/binaural distinction, were seen in the dynamic range and minimum latency. Interanimal differences seen in the responses of the efferent neurons may be related to differences in the level of anesthesia.

Acoustic Stimulation↗

PubMed1986

Single unit clues to cochlear mechanisms.

In recent years studies on isolated hair cells have suggested that there is an inherent tuning of hair cells determined by their mechanical and electrical properties. However, tuning for mammalian cochleas appears to be much more complicated since there are typically two types of receptor cells (inner and outer hair cells) imbedded in a highly organized framework of supporting cells, membranes and fluids. The major neural output of the cochlea can be monitored by recording the activity of myelinated axons of spiral ganglion cells, not only under normal conditions, but also when the discharge patterns are altered by ototoxic drugs, acoustic trauma or olivocochlear bundle stimulation. A model system with two excitatory influences, one sharply tuned and highly sensitive, and a second, broadly tuned and relatively insensitive, can account for much of the existing data. Results from single-neuron marking studies support the notion that these two influences probably involve interactions between inner and outer hair cells. More global influences such as the endocochlear potential also can act on auditory-nerve fibers through the hair-cell systems. Thus, the inherent frequency selectivity of the receptor cell is only one of many factors that determine the tuning of mammalian auditory-nerve fibers.

Adaptation, Physiological↗

PubMed1985

Applications of neuronal labeling techniques to the study of the peripheral auditory system.

Horseradish peroxidase (HRP) techniques have recently been applied to the study of the peripheral auditory system. These techniques make it possible to trace single, auditory-nerve fibers from their peripheral terminals on sensory cells to their central terminations within the cochlear nucleus. For the large, myelinated axons of type-I neurons contacting inner hair cells, HRP can be injected intracellularly through the same electrode used to record neural activity, allowing correlations to be made between structure and function on a single-cell basis. From these data, a cochlear frequency map has been constructed, and morphological correlates of differences in spontaneous discharge have been identified. For the small, unmyelinated axons of type-II neurons contacting outer hair cells, single-unit recordings have not yet been made; however, these neurons have been labeled by gross extracellular injections of HRP. Extracellular injections have also been used to study the peripheral terminations of single efferent neurons projecting to the outer hair cell region. The afferent fibers to the outer hair cell (OHC) region contact primarily OHCs from the third row, while efferent fibers primarily contact cells from the first row. Single efferent fibers innervate OHCs over a significantly larger cochlear length than single afferent fibers of either type. Possible functional interpretations of these morphological differences are discussed.

Animals↗

PubMed1984

The central projections of intracellularly labeled auditory nerve fibers in cats.

The central projections of physiologically characterized auditory nerve fibers were studied in the cochlear nuclei of adult cats after intracellular staining with horseradish peroxidase (HRP). This technique consistently labels only the type I spiral ganglion neurons which contact inner hair cells in the cochlea (Liberman and Oliver, '84). The central axon of each type I neuron bifurcates in the cochlear nucleus to form an ascending branch and a descending branch. The characteristic frequency (CF) of a fiber corresponds to the dorsoventral position of these major branches and their collateral ramifications within the nucleus. Fibers of low CFs are distributed ventrally, and fibers of increasing CF are distributed progressively more dorsally. In some cases, the collateral branches deviate from this tonotopic arrangement, particularly in (1) the octopus cell region of the posteroventral cochlear nucleus, (2) the zone of bifurcations of the auditory nerve fibers, and (3) the anterior, dorsal, and lateral margins of the ventral cochlear nucleus. Spontaneous discharge rate (SR) is related to the complexity of the axon arbor, especially along the ascending branch. Fibers of low and medium SR exhibit more axonal branch points and longer collateral lengths than do those with high SR. Six of 37 labeled fibers fail to innervate the dorsal cochlear nucleus, a feature apparently unrelated to CF or SR.

Afferent Pathways↗

PubMed1984

Morphometry of intracellularly labeled neurons of the auditory nerve: correlations with functional properties.

Single auditory-nerve fibers were injected with horseradish peroxidase after their tuning properties, characteristic frequencies, and spontaneous discharge rates were measured. From these functional properties virtually all other aspects of auditory-nerve response can be predicted. Labeled fibers were reconstructed from the point of peripheral termination on cochlear hair cells to the point at which they enter the cochlear nucleus. Several morphological properties were measured at the light-microscopic level, including axonal diameter, axonal length, internodal distances, cell-body area, and cell-body shape. All of these parameters were correlated, though some weakly, with characteristic frequency. However, only axonal diameter was correlated with spontaneous discharge rate.

Animals↗