Tunnel crossing fibers and their synaptic connections within the inner hair cell region in the organ of corti in the maturing mouse

 Combined ultrastructural and immunocytochemical studies reveal that in the adolescent 12- to 17-day-old mouse the afferent tunnel crossing fibers that innervate outer hair cells receive synaptic contacts from three distinct sources: the GABAergic fibers (GABA= gamma-aminobutyric acid) of the lateral olivocochlear bundle, the non-GABAergic efferent tunnel crossing fibers, and the inner hair cells themselves. The GABAergic fibers give off collaterals that synapse with the afferent tunnel fibers as they cross the inner hair cell region. These collaterals also form synapses with afferent radial dendrites that are synaptically engaged with the inner hair cells. Vesiculated varicosities of nonGABAergic efferent tunnel fibers also synapse upon the outer spiral afferents. Most of this synaptic activity occurs within the inner pillar bundle. Distinctive for this region are synaptic aggregations in which several neuronal elements and inner hair cells are sequentially interconnected. Finally, most unexpected were the afferent ribbon synapses that inner hair cells formed en passant on the shafts of the apparent afferent tunnel fibers. The findings indicate that: (1) the afferent tunnel (i.e., outer spiral) fibers may be postsynaptic to both the inner and the outer hair cells; (2) the non-GABAergic efferent and the afferent tunnel fibers form extensive synaptic connections before exiting the inner pillar bundle; (3) the GABAergic component of the lateral olivocochlear system modulates synaptically both radial and outer spiral afferents. Accepted: 7 May 1998     

Two-tone suppression in the basilar membrane of the cochlea: mechanical basis of auditory-nerve rate suppression.

1. The vibratory response to two-tone stimuli was measured in the basilar membrane of the chinchilla cochlea by means of the M?ssbauer technique or laser velocimetry. Measurements were made at sites with characteristic frequency (CF, the frequency at which an auditory structure is most sensitive) of 7-10 kHz, located approximately 3.5 mm from the oval window. 2. Two-tone suppression (reduction in the response to one tone due to the presence of another) was demonstrated for CF probe tones and suppressor tones with frequencies both higher and lower than CF, at moderately low stimulus levels, including probe-suppressor combinations for which responses to the suppressor were lower than responses to the probe tone alone. 3. For a fixed suppressor tone, suppression magnitude decreased as a function of increasing probe intensity. 4. The magnitude of suppression increased monotonically with suppressor intensity. 5. The rate of growth of suppression magnitude with suppressor intensity was higher for suppressors in the region below CF than for those in the region above CF. 6. For low-frequency suppressor tones, suppression magnitude varied periodically, attaining one or two maxima within each period of the suppressor tone. 7. Suppression was frequency tuned: for either above-CF or below-CF suppressor tones, suppression magnitude reached a maximum for probe frequencies near CF. 8. Cochlear damage or death diminished or abolished suppression. There was a clear positive correlation between magnitude of suppression and basilar-membrane sensitivity for responses to CF tones. 9. Suppression tended to be accompanied by small phase lags in responses to CF probe tones. 10. Because all of the features of two-tone suppression at the basilar membrane match qualitatively (and, generally, also quantitatively) the features of two-tone rate suppression in auditory-nerve fibers, it is concluded that neural two-tone rate suppression originates in mechanical phenomena at the basilar membrane. 11. Because the lability of mechanical suppression parallels the loss of sensitivity and frequency tuning due to outer hair cell dysfunction, the present findings suggest that mechanical two-tone suppression arises from an interaction between the outer hair cells and the basilar membrane.     

Functional properties of auditory-nerve fibers during postnatal development in the kitten

Summary The discharges of the auditory-nerve fibers were studied in kittens between 2–40 days of age. Up to the 10th postnatal day, fibers could be divided into two main categories: (1) fibers with spontaneous activity (SA) that respond to sound and (2) fibers without SA but with evoked responses. A third, smaller, category, fibers having neither SA nor evoked activity, was also present. The development of SA comprises two phases. The first, lasting from birth up to the third postnatal week, shows a relatively fast increase and the second, lasting up to adulthood, a slower increase. Typical tone burst responses can be recorded at the end of the first postnatal week. Thereafter reactivity steadily increases especially after the 10th postnatal day. In young animals, rate level function is characterized by a steep segment with a low dynamic range followed by a decrease in activity that lasts until the end of the second week. At this point adult-like functions may be observed, although maximal firing still increases for some weeks. Tuning curves and threshold sensitivity tend to develop inversely at corresponding frequencies. Fibers with low characteristic frequencies reach adult threshold before that of high frequency fibers and high frequency fibers reach adult tuning before low frequency fibers. A comparison of auditory-nerve fiber activity in kittens show that maturation of most functional characteristics lasts several weeks after birth and in some cases continues after the first postnatal month.     

Responses of medial olivocochlear neurons

Medial olivocochlear (MOC) neurons project to outer hair cells (OHC), forming the efferent arm of a reflex that affects sound processing and offers protection from acoustic overstimulation. The central pathways that trigger the MOC reflex in response to sound are poorly understood. Insight into these pathways can be obtained by examining the responses of single MOC neurons recorded from anesthetized guinea pigs. Response latencies of MOC neurons are as short as 5 ms. This latency is consistent with the idea that type I, but not type II, auditory-nerve fibers provide the major inputs to the reflex interneurons in the cochlear nucleus. This short latency also implies that the cochlear-nucleus interneurons have rapidly conducting axons. In the cochlear nucleus, lesions of the posteroventral subdivision (PVCN), but not the anteroventral (AVCN) or dorsal (DCN) subdivisions, produce permanent disruption of the MOC reflex, based on a metric of adaptation of the distortion-product otoacoustic emission (DPOAE). This finding supports earlier anatomical results demonstrating that some PVCN neurons project to MOC neurons. Within the PVCN, there are two general types of units when classified according to poststimulus time histograms: onset units and chopper units. The MOC response is sustained and cannot be produced solely by inputs having an onset pattern. The MOC reflex interneurons are thus likely to be chopper units of PVCN. Also supporting this conclusion, chopper units and MOC neurons both have sharp frequency tuning. Thus, the most likely pathway for the sound-evoked MOC reflex begins with the responses of hair cells, proceeds with type I auditory-nerve fibers, PVCN chopper units, and MOC neurons, and ends with the MOC terminations on OHC.     

Development of responses to acoustic interaural intensity differences in the cat inferior colliculus

Summary Responses of single neurones in the inferior colliculus of anaesthetized adult cats and kittens were studied using best-frequency stimuli of varying interaural intensity difference (IID). Two broad classes of neurone, distinguished by the predominant type of input from each ear, were examined. One class of cells received predominantly excitatory input from each ear (EE cells). The other class were excited by monaural stimulation of the contralateral ear and showed no response to monaural stimulation of the ipsilateral ear, but inhibition of the excitatory response by simultaneous ipsilateral stimulation (EI cells). Fourteen of the 18 adult EI cells showed marked changes in discharge rate with variation in IID. Adult EI cells showed low response variability and were insensitive to changes in average binaural intensity. In all cases of IID sensitivity, the onset component of the response was less sensitive to IID than the sustained component. Eight out of ten EE cells were insensitive to IID over the range tested. Cells of high best-frequency in kittens younger than 28 days showed irregular changes in discharge rate with variation in IID and wide response variability. Some low-frequency EI cells in young kittens showed sensitivity to IID, but it is unlikely that these could be involved in sound localization as their frequency response was inappropriate. Many cells in kittens aged 31–40 days showed monotonic, adult-like IID functions, but the response variability of these cells remained higher than that of adult cat neurones. These data provide evidence for a developmental change of binaural interaction in the cat.     

Sharpened cochlear tuning in a mouse with a genetically modified tectorial membrane

Frequency tuning in the cochlea is determined by the passive mechanical properties of the basilar membrane and active feedback from the outer hair cells, sensory-effector cells that detect and amplify sound-induced basilar membrane motions. The sensory hair bundles of the outer hair cells are imbedded in the tectorial membrane, a sheet of extracellular matrix that overlies the cochlea's sensory epithelium. The tectorial membrane contains radially organized collagen fibrils that are imbedded in an unusual striated-sheet matrix formed by two glycoproteins, alpha-tectorin (Tecta) and beta-tectorin (Tectb). In Tectb(-/-) mice the structure of the striated-sheet matrix is disrupted. Although these mice have a low-frequency hearing loss, basilar-membrane and neural tuning are both significantly enhanced in the high-frequency regions of the cochlea, with little loss in sensitivity. These findings can be attributed to a reduction in the acting mass of the tectorial membrane and reveal a new function for this structure in controlling interactions along the cochlea.     

Immunoelectron microscopy identifies several types of GABA-containing efferent synapses in the guinea-pig organ of Corti

Using an immunoperoxidase technique, we have localized by light and electron microscopy GABA-immunostained fibers within a component of the efferent innervation of the organ of Corti. At the light microscopic level, GABA-immunostained fibers were observed within the inner spiral bundle (below the inner hair cells) and the tunnel spiral bundle. The immunostaining was clearly more intense in the upper turns than in the basal turns. Mostly in the upper turns, GABA-immunostained fibers were seen crossing the tunnel of Corti to reach the outer hair cells where they formed large immunostained patches at the base of the cells. Unevenly distributed throughout these upper turns, immunostained fibers were seen climbing along the outer hair cells and traveling near the non-sensorineural Hensen's cells. The electron microscopic observations of GABA-immunostained fibers in the upper turns allowed us to identify within the inner spiral bundle vesiculated varicosities synapsing with radial dendrites connected to the inner hair cells. In the outer hair cell area, the GABA-immunostained fibers made several kinds of synaptic contacts. They included a minor population of the large axosomatic synapses with the basal pole of the outer hair cells and many axodendritic synapses with the spiral dendrites connected to these cells. Occasionally, the GABA-immunostained climbing fibers also synapsed with the outer hair cells at a supranuclear level. These result confirm previous light microscopic data dealing with the projection of the GABA-immunostained fibers along the cochlear partition. Moreover, they extend them in characterizing several kinds of GABA-immunostained synapses. These latter findings agree with previous neurochemical electrophysiological data which suggests an efferent neurotransmitter role for GABA. Nevertheless, such an existence of an efferent innervation predominantly projecting to the upper turns of the cochlea adds another criterion distinguishing the "apical" from the "basal" cochlea.     

Effects of illumination on auditory threshold.

Auditory thresholds of four squirrel monkeys were examined with a 4 kHz tone in light and dark ambient sensory conditions. The results revealed that auditory sensitivity is higher in the light than in the dark.     

Differences in mechano-transducer channel kinetics underlie tonotopic distribution of fast adaptation in auditory hair cells

The first step in audition is a deflection of the sensory hair bundle that opens mechanically gated channels, depolarizing the sensory hair cells. Two mechanism of adaptation of mechano-electric transducer (MET) channels have been identified in turtle auditory hair cells. The rate of fast adaptation varies tonotopically and is postulated to underlie a mechanical tuning mechanism in turtle auditory hair cells. Fast adaptation is driven by a calcium-dependent feedback process associated with MET channels. The purpose of this paper is to test the hypothesis that fast adaptation contributes to MET channel kinetics and that variations in channel kinetics underlie the tonotopic distribution of fast adaptation. To test for kinetic differences, the open channel blocker dihydrostreptomycin (DHS) was used. DHS blocked MET currents from low-frequency cells (IC(50) = 14 +/- 2 microM) more effectively than high-frequency cells (IC(50) = 75 +/- 5 microM), suggesting differences in MET channel properties. DHS block showed similar calcium sensitivities at both papilla locations. No difference in calcium permeation or block of the transducer channels was observed, indicating that the DHS effect was not due to differences in the channel pore. Slowing adaptation increased DHS efficacy, and speeding adaptation decreased DHS efficacy, suggesting that adaptation was influencing DHS block. DHS block of MET channels slowed adaptation, most likely by reducing the peak intraciliary calcium concentration achieved, supporting the hypothesis that the rate of adaptation varies with the calcium load per stereocilia. Another channel blocker, amiloride showed similar efficacy for high- and low-frequency cells with an IC(50) of 24.2 +/- 0.5 microM and a Hill coefficient of 2 but appeared to block high-frequency channels faster than low-frequency channels. To further explore MET channel differences between papilla locations, stationary noise analysis was performed. Spectral analysis of the noise gave half power frequencies of 1,185 +/- 148 Hz (n = 6) and 551 +/- 145 Hz (n = 5) for high- and low-frequency cells in 2.8 mM external calcium. The half power frequency showed similar calcium sensitivity to that of adaptation shifting to 768 +/- 205 Hz (n = 4) and 289 +/- 63 Hz (n = 4) for high- and low-frequency cells in 0.25 mM external calcium. Both the pharmacological data and the noise analysis data are consistent with the hypothesis that the tonotopic distribution of fast adaptation is in part due to differences in MET channel kinetics. An increase in the number of MET channels per stereocilia (termed summation) and or intrinsic differences in MET channel kinetics may be the underlying mechanism involved in establishing the gradient.     

Velocity- and acceleration-sensitive units in the trunk lateral line of the trout.

1. The two main types of lateral line organs of lower vertebrates are the superficial neuromasts (SN), with a cupula that protrudes in the surrounding water, and the canal neuromasts (CN), located in the lateral line canal. The scales of the trunk lateral line canal of fish contain SNs as well as CNs. In this study, we examine whether there exist two functional classes of afferent fibers in the trunk lateral line nerve of the rainbow trout that can be attributed to the SNs and CNs. 2. The response properties of the afferent fibers in the trunk lateral line nerve have been determined during stimulation with sinusoidally varying water motion generated by a small vibrating sphere. Linear frequency response analysis revealed the presence of two distinct populations of afferent fibers in the lateral line nerve. The fibers belonging to the two populations showed significant differences in the frequency at which the sensitivity was maximal, the low-frequency response slope and the low-frequency asymptotic phase angle. 3. One population of fibers has a maximum sensitivity at 36 +/- 13 (SD) Hz (n = 22) and responds up to this frequency to water velocity. The low-frequency slope of the frequency response of these fibers was 20 +/- 3 (SD) dB/decade and the low-frequency phase lead was 121 +/- 11 degrees (mean +/- SD), both with respect to sphere displacement. The fibers of the other population have a maximum sensitivity at 93 +/- 14 (SD) Hz (n = 12) and respond up to this frequency to water acceleration. The low-frequency slope of these fibers was 35 +/- 5 (SD) dB/decade, and the low-frequency phase lead was 188 +/- 13 degrees (mean +/- SD). 4. Analysis of the stochastic properties of the spontaneous activity of both types of fibers revealed that the mean firing rate of the fibers responding to water velocity (26 +/- 12 spikes/s, mean +/- SD; n = 22) was significantly higher than that of the fibers responding to acceleration (36 +/- 11 spikes/s, mean +/- SD; n = 12). The other statistical properties of the spontaneous activity were found to be indistinguishable. 5. From comparison of the results with the available quantitative data on frequency responses of lateral line organs in other species, it has been concluded that the fibers responding (< or = 40 Hz) to water velocity innervate SNs and that the fibers responding (< or = 90 Hz) to water acceleration innervate CNs.(ABSTRACT TRUNCATED AT 400 WORDS)     

儿童感音神经性聋听觉稳态诱发反应阈与听性脑干反应阈比较

目的研究听觉稳态诱发反应(ASSR)和听性脑干反应(ABR)阈与纯音听阈的差别和相关性。方法选择74例儿童感音神经性聋患者(118耳)分别进行ASSR、ABR和电测听检查,比较ASSR、ABR反应阈及纯音听阈,同时就ASSR、ABR反应阈与纯音听阈进行相关性分析。结果 ASSR和ABR反应阈与纯音听阈均有良好的相关性。ABR的反应阈与纯音听阈阈值接近,而ASSR反应阈与纯音听阈间差值较大。ASSR反应阈与纯音听阈间的相关性要优于ABR反应阈与纯音听阈间的相关性。结论 ASSR和ABR均为较好的评估行为听阈的客观测听方法。     

Developmental change in auditory selective attention as reflected by phasic heart rate changes

Heart rate was recorded from five different groups of children (ages 7, 10, 12, 14, and 20 years) while they were performing an auditory selective attention task. The participants were instructed to count rare tone pips embedded in a series of standard tone pips presented at one (attended) ear while ignoring rare and standard stimuli presented at the other (unattended) ear. A pattern of anticipatory heart rate deceleration followed by acceleration was associated with rare tone pips at the attended ear but not with rare tone pips that should be ignored. The absence of differential sensitivity of heart rate responses to rare tone pips presented at the unattended ear was observed for all age groups. These findings were interpreted to suggest that the ability to ignore irrelevant target stimuli has reached mature levels during middle childhood. The depth of anticipatory deceleration increased until age 14, suggesting that the ability to maintain attentional set continues to develop beyond childhood.     

On the presence of reciprocal synapses in the paratympanic organ of the chicken

Summary The innervation pattern of the paratympanic organ was studied by TEM. The paratympanic organ is a small tapering vesicle, typical of birds, situated in the medial wall of the tympanic cavity; it contains hair cells which are similar to type II receptors of the acoustic-lateral system; these cells are characterised by synapses which are not only afferent and efferent, as previously described, but also reciprocal with efferent fibers.Our observation revealed some efferent nerve fibers which form a relationship with hair cells containing synaptic bodies situated next to the plasma membrane and near the fibers themselves. Since synaptic bodies are commonly considered to be the site where the transmission of the impulse from the receptor to the nerve fiber takes place, our pictures suggest that the efferent fibers and hair cells may be either presynaptic or postsynaptic with respect to each other in the paratympanic organ. The hypothesis is formulated that reciprocal synapses allow interaction between hair cells, thus determining an increase in the contrast of information sent by the paratympanic organ to the CNS.     

Determinants of spatial and temporal coding by semicircular canal afferents

The vestibular semicircular canals are internal sensors that signal the magnitude, direction, and temporal properties of angular head motion. Fluid mechanics within the 3-canal labyrinth code the direction of movement and integrate angular acceleration stimuli over time. Directional coding is accomplished by decomposition of complex angular accelerations into 3 biomechanical components-one component exciting each of the 3 ampullary organs and associated afferent nerve bundles separately. For low-frequency angular motion stimuli, fluid displacement within each canal is proportional to angular acceleration. At higher frequencies, above the lower corner frequency, real-time integration is accomplished by viscous forces arising from the movement of fluid within the slender lumen of each canal. This results in angular velocity sensitive fluid displacements. Reflecting this, a subset of afferent fibers indeed report angular acceleration to the brain for low frequencies of head movement and report angular velocity for higher frequencies. However, a substantial number of afferent fibers also report angular acceleration, or a signal between acceleration and velocity, even at frequencies where the endolymph displacement is known to follow angular head velocity. These non-velocity-sensitive afferent signals cannot be attributed to canal biomechanics alone. The responses of non-velocity-sensitive cells include a mathematical differentiation (first-order or fractional) imparted by hair-cell and/or afferent complexes. This mathematical differentiation from velocity to acceleration cannot be attributed to hair cell ionic currents, but occurs as a result of the dynamics of synaptic transmission between hair cells and their primary afferent fibers. The evidence for this conclusion is reviewed below.     

The effect of aging on EEG brain oscillations related to sensory and sensorimotor functions

PurposeThe question of the present study is whether the brain as a system with gradually decreasing resources maximizes its performance by reorganizing neural networks for greater efficiency.Material/methodsAuditory event-related low frequency oscillations (delta δ – [2, 4] Hz; theta θ – [4.5, 7] Hz; alpha α – [7.5, 12] Hz) were examined during an auditory discrimination motor task (low-frequency tone – right hand movement, high-frequency tone – left hand movement) between two groups with mean age 26.3 and 55 years.ResultsThe amplitudes of the phase-locked δ, θ and α activity were more pronounced with a progressive increase in age during the sensory processing, independent of tone type. The difference between the groups with respect to scalp distribution was tone-independent for delta/theta oscillations, but not for the alpha activity. Age-related and tone-dependent changes in α band activity were focused at frontal and sensorimotor areas. Neither functional brain specificity was observed for the amplitudes of the low-frequency (δ, θ, α) oscillations during the cognitive processing, which diminished with increasing age.ConclusionThe cognitive brain oscillatory specificity diminished with increasing age.     

The Cochlear Spiral Ganglion Neurons: The Auditory Portion of the VIII Nerve

The VIII nerve is formed by sensory neurons that innervate the inner ear, i.e., the vestibular and the auditory receptors. Neurons of the auditory portion, the cochlear afferent fibers that innervate the sensory hair cells of the organ of Corti, have their somas in the cochlear spiral ganglion where two types of neurons can be distinguished. Afferent Type-I neurons are the 95% of the total population. Bipolar and myelinated fibers, each one innervates only one cochlear inner hair cell (IHC). In contrast, afferent Type-II neurons are only the 5% of the spiral ganglion population. They are pseudounipolar and unmyelinated fibers and innervate the cochlear outer hair cells (OHC) so that one afferent Type-II fiber contacts with multiple OHCs, but each OHC only receives one contact from one Type-II neuron. Both types of VIII nerve fibers are glutamatergic, but these asymmetric innervations of the cochlear sensory cells could suggest that the IHC codifies the truly auditory message but the OHC only informs about mechanical aspects of the state of the organ of Corti. In fact, the central nervous system (CNS) has control over the information transmitted by the Type-I neuron by means of axons from the superior olivary complex that innervate them to modulate, filter and/or inhibit the entry of auditory message to CNS. The aim of this paper is to review the current knowledge about the anatomy and physiology of the auditory portion of the VIII nerve. Anat Rec, 302:463–471, 2019. © 2018 Wiley Periodicals, Inc.     

The development of innervation patterns in the avian cochlea

The sequence of developmental events leading to the innervation of the cochlea and the differentiation of its receptor cells has been studied in chick embryos with Golgi methods. We describe the morphogenesis of cochlear ganglion cell peripheral processes from their appearance in early embryos to the formation of their mature endings on hair cells in the basilar papilla (organ of Corti) of prehatching chicks. In the stage of peripheral fiber outgrowth, embryonic days 3-5, the fibers emerge from the ganglion cell bodies and grow, in a uniform fashion, toward the undifferentiated receptor epithelium of the otocyst. In the stage of the invasion of the otocyst by the peripheral fibers, embryonic days 6-7, some fibers enter the epithelium directly after reaching it, others enter after traveling some distance longitudinally beneath its basal lamina. The invading fibers appear to encounter resistance at the basal lamina, but, once within the epithelium, at embryonic days 8-9, they form a surfeit of branches in columnar zones oriented radially toward the surface. In early synaptogenesis (embryonic days 8-9) hair cells first become apparent. They differentiate from primitive epithelial cells. These cells withdraw their basal processes, which appear to accompany the growing fibers into the superficial epithelium. At embryonic days 11-13, the stage of mid-synaptogenesis, the fibers develop large, bulbous, preterminal and terminal swellings, which are located below the bases of the hair cells; the surplus branches atrophy or withdraw. Efferent axons are first seen in the epithelium at this time. In late synaptogenesis (embryonic days 14-17), the preterminal swellings disappear and the endings transform into mature foot-shapes at the bases of the hair cells. These morphological changes during the development of the peripheral endings are comparable to those of cochlear axons in nucleus magnocellularis (cochlear nucleus). During mid-synaptogenesis, when the ganglion cells develop swellings in the periphery, their central axons ramify extensively. Late in synaptogenesis, while the peripheral swellings disappear, there is a corresponding condensation of the central terminals to form the end-bulbs of Held. Thus, specific connections of the cochlear ganglion cells and their target cells in the ear and brain may result from two sequential developmental phases: (1) loosely organized and overabundant initial growth of branches from the fibers entering their target tissue; (2) reorganization of these fibers with the disappearance or resorption of the surplus branches during the transformation of their endings into mature synaptic arrangements.(ABSTRACT TRUNCATED AT 400 WORDS)     

Binaural interaction in low-frequency neurons in inferior colliculus of the cat. I. Effects of long interaural delays, intensity, and repetition rate on interaural delay function

Detailed, quantitative studies were made of the interaural phase sensitivity of 197 neurons with low best frequency in the inferior colliculus (IC) of the barbiturate-anesthetized cat. We analyzed the responses of single cells to interaural delays in which tone bursts were delivered to the two ears via sealed earphones and the onset of the tone to one ear with respect to the other was varied. For most (80%) cells the discharge rate is a cyclic function of interaural delay at a period corresponding to that of the stimulating frequency. The cyclic nature of the interaural delay curve indicates that these cells are sensitive to the interaural phase difference. These cells are distributed throughout the low-frequency zone of the IC, but they are less numerous in the medial and caudal zones. Cells with a wide variety of response patterns will exhibit interaural phase sensitivities at stimulating frequencies up to 3,100 Hz, although above 2,500 Hz the number of such cells decrease markedly. Using dichotic stimuli we could study the cell's sensitivity to the onset delay and interaural phase independently. The large majority of IC cells respond only to changes in interaural phase, with no sensitivity to the onset delay. However, a small number (7%) of cells exhibit a sensitivity to the onset delay as well as to the interaural phase disparity, and most of these cells show an onset response. The effects of changing the stimulus intensity equally to both ears or of changing the interaural intensity difference on the mean interaural phase were studied. While some neurons are not affected by level changes, others exhibit systematic phase shifts for both average and interaural intensity variations, and there is a continuous distribution of sensitivities between these extremes. A few cells also showed systematic changes in the shape of the interaural delay curves as a function of interaural intensity difference, especially at very long delays. These shifts can be interpreted as a form of time-intensity trading. A few cells demonstrated orderly changes in the interaural delay curve as the repetition rate of the stimulus was varied. Some of these changes are consonant with an inhibitory effect that occurs at stimulus offset. The responses of the neurons show a strong bias for stimuli that would originate from he contralateral sound field; 77% of the responses display mean interaural phase angles that are less than 0.5 of a cycle, which are delays to the ipsilateral tone.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanical response of frog saccular hair bundles to the aminoglycoside block of mechanoelectrical transduction.

1. Deflections of the mechanosensory hair bundles on frog saccular hair cells were measured interferometrically, with submillisecond temporal and submicrometer spatial resolution, and with subnanometer displacement sensitivity. 2. The direction of the initial bundle deflection (toward the taller stereocilia) in response to a sudden application of aminoglycoside antibiotics shows that the mechanosensory channels are blocked in their mechanically open state. 3. The magnitude of the initial deflection is consistent with published data on the gating swing as derived from the gating compliance. 4. A delayed relaxation and frequently a reversal of the initial deflection were observed and are attributed to the previously reported mechanical adaptation mechanism, which is at least partially controlled by the influx of Ca2+ through the transduction channels. 5. Increases of low-frequency spontaneous motion were found at intermediate blocker concentrations. They can be well accounted for by the fluctuating force exerted on the bundle by the random binding and unbinding of blocker molecules. 6. The mechanical response of the hair bundle to aminoglycosides may be related to their acute and specific ototoxicity.