HYPOTHESIS Mechanical stimulation through a cochlear third window into the scala tympani in a chinchilla model with normal and fixed stapes can generate cochlear responses equivalent to acoustic stimuli. BACKGROUND Cochlear stimulation via the round window (RW) using active middle ear implants (AMEIs) can produce physiologic responses similar to acoustic stimulation including in a model of stapes fixation. However, pathologic conditions, such as advanced otosclerosis, can preclude delivery of sound energy to the cochlea through the oval window and/or the RW. METHODS Cochlear microphonic (CM) and laser Doppler vibrometer measurements of stapes and RW velocities were performed in 6 ears of 4 chinchillas. Baseline measurements to acoustic sinusoidal stimuli (0.25-8 kHz) were made. Measurements were repeated with an AMEI driving the RW or a third window to the scala tympani before and after stapes fixation. RESULTS AMEI stimulation of the third window produced CM waveforms with morphologies similar to acoustic stimuli. CM thresholds with RW and third-window stimulation were frequency dependent but ranged from 0.25 to 10 and 0.5 to 40 mV, respectively. Stapes fixation, confirmed by laser Doppler vibrometer measurements, resulted in a significant frequency dependent impairment in CM thresholds up to 13 dB (at <3 kHz) for RW stimulation and a nonsignificant frequency-dependent improvement of up to 10 dB (at >3 kHz) via third-window stimulation. CONCLUSION AMEI mechanical stimulation through a third window into the scala tympani produces physiologic responses nearly identical to acoustic stimulation including in a model of stapes fixation with decreased efficiency.

Basilar-membrane responses to single tones were measured, using laser velocimetry, at a site of the chinchilla cochlea located 3.5 mm from its basal end. Responses to low-level (< 10-20 dB SPL) characteristic-frequency (CF) tones (9-10 kHz) grow linearly with stimulus intensity and exhibit gains of 66-76 dB relative to stapes motion. At higher levels, CF responses grow monotonically at compressive rates, with input-output slopes as low as 0.2 dB/dB in the intensity range 40-80 dB. Compressive growth, which is significantly correlated with response sensitivity, is evident even at stimulus levels higher than 100 dB. Responses become rapidly linear as stimulus frequency departs from CF. As a result, at stimulus levels > 80 dB the largest responses are elicited by tones with frequency about 0.4-0.5 octave below CF. For stimulus frequencies well above CF, responses stop decreasing with increasing frequency: A plateau is reached. The compressive growth of responses to tones with frequency near CF is accompanied by intensity-dependent phase shifts. Death abolishes all nonlinearities, reduces sensitivity at CF by as much as 60-81 dB, and causes a relative phase lead at CF.

1. The relation between the response properties of semicircular canal afferents and their peripheral innervation patterns was studied by the use of intra-axonal labeling techniques. Fifty physiologically characterized units were injected with horseradish peroxidase (HRP) or Lucifer yellow CH (LY) and their processes were traced to the crista. The resting discharge, discharge regularity, and responses to both externally applied galvanic currents and sinusoidal head rotations were determined for most neurons. Terminal fields were reconstructed and, as in the preceding paper, the fibers were classified as calyx, bouton, or dimorphic units. 2. To determine if the intra-axonal sample was representative, the physiological properties of the labeled units were compared with those of a sample of extracellularly recorded units. A comparison was also made between the morphology of the intra-axonal units and those labeled by extracellular injection of HRP into the vestibular nerve Most of the discrepancies between the intra-axonal and the two extracellular samples can be explained by assuming that small-diameter fibers are underrepresented in the former sample. 3. A normalized coefficient of variation (CV*), independent of discharge rate, was used to classify units as regular, intermediate, or irregular. The CV* ranged from 0.020 to 0.60. Regular units (CV* less than or equal to 0.10) outnumbered irregular units (CV* greater than or equal to 0.20) by an approximately 3:1 ratio and had higher resting discharges. 4. Calyx units were invariably irregular. The one recovered bouton unit was regular. The discharge regularity of dimorphic units was related to their epithelial location, with those found in the periphery of the crista having a more regular discharge than those located more centrally. Dimorphic units, even those with quite similar morphology, can differ in their discharge regularity. Calyx and dimorphic units, which differ in their morphology, can both be irregular. These observations imply that discharge regularity is not determined by the branching pattern of a fiber or the number and types of hair cells it contacts. 5. The galvanic sensitivity (beta*) of an afferent, irrespective of its peripheral innervation pattern, was strongly correlated with CV*. This is consistent with the notion that discharge regularity and galvanic sensitivity are causally related, both being determined by postspike recovery mechanisms of the afferent nerve terminal.(ABSTRACT TRUNCATED AT 400 WORDS)

Four chinchillas were trained to respond differently to /t/ and /d/ consonant-vowel syllables produced by four talkers in three vowel contexts. This training generalized to novel instances, including synthetically produced /da/ and /ta/(voice-on-set times of 0 and +80 milliseconds, respectively). In a second experiment, synthetic stimuli with voice-onset times between 0 and +80 milliseconds were presented for identification. The form of the labeling functions and the "phonetic boundaries" for chinchillas and English-speaking adults were similar.

The collection of compound action potential (AP) threshold curves and their use to define the sensitivity of individual animals are described. Forward masking AP tuning curves (APTC) have also been collected in the chinchilla. Characteristics of APTCs are compared with single fiber frequency-threshold curves (FTC) in the same group of animals. The two sets of data are quite similar when the probe frequency used to collect the APTC is equated with a fiber's characteristic frequency (CF). The major difference is that APTCs are usually broader than FTCs. A paradigm utilizing two maskers in a forward masking situation, developed to study psychophysical unmasking [19,37], has been modified for measuring AP suppression. AP suppression areas are described as similar to single fiber two-tone suppression areas when probe frequency and CF are above 3 kHz. Relationships among single fiber, AP and psychophysical thresholds, tuning curves and suppression areas are discussed.

1. Extracellular recording techniques were used in the chinchilla to study the discharge properties of utricular afferents, including their discharge regularity, background discharge, and responses to both externally applied galvanic currents and centrifugal forces. 2. A normalized coefficient of variation (CV*), independent of discharge rate, was used to classify units as regularly (CV* less than 0.10), intermediate (0.10 less than or equal to CV* less than or equal to 0.20), or irregularly discharging (CV* greater than 0.20). In some circumstances, it was useful to recognize a group of very regularly discharging afferents (CV* less than 0.05). The CV* ranged from less than 0.020 to greater than 0.60. Regular units outnumbered irregular units by an approximate 3:1 ratio. The distribution of CV*s was bimodal: there was a major peak at CV*= 0.03 and a minor peak at CV*= 0.3. 3. Background rates were measured with the head in a horizontal position. Those of regular units usually fell between 40 and 80 spikes/s (mean: 54 spikes/s); those of irregular units were more broadly distributed (mean: 47 spikes/s). 4. Units were categorized in terms of the tilt directions resulting in increased discharge. There is a broad distribution of excitatory tilt directions with some units excited by ipsilateral rolls, others by contralateral rolls, some by nose-up pitches, and still others by nose-down pitches. In the chinchilla, there are almost equal numbers of units excited by ipsilateral or contralateral tilts. This is in contrast to previous findings in the cat and squirrel monkey, where the former units predominant by a 3:1 ratio. The difference can be related to the fact that the medial zone of the macula, where units excited by ipsilateral tilts reside, makes up a smaller proportion of the sensory epithelium in the chinchilla than in the monkey. 5. Galvanic sensitivity (beta *) and discharge regularity (CV*) were related by a power law, beta*=(CV*), with an exponent, b = 0.70. 6. Responses to sinusoidal centrifugal forces in the frequency range, f, between DC and 2 Hz were characterized by their gains (gf) and phases (phi f), taken with respect to peak linear force. Response linearity was studied by varying the amplitude of a 0.1-Hz sinusoid from 0.05 to 0.4 g. Nonlinear distortion was small (approximately 10%), as was the variation of gain (+/- 10%) and phase (+/- 5 degrees) with amplitude. 7. Response dynamics vary with discharge regularity. Very regular units are tonic. Their gains are typically 50 spikes.s-1/g and almost constant (+/- 10%) over the entire frequency range. Phases hover near zero with small (5 degrees) phase leads at low frequencies and slightly larger (10 degrees) phase lags at high frequencies. Irregular units are more phasic.(ABSTRACT TRUNCATED AT 400 WORDS)

1. The relation between the discharge properties of utricular afferents and their peripheral innervation patterns was studied in the chinchilla by the use of intra-axonal labeling techniques. Fifty-three physiologically characterized units were injected with horseradish peroxidase (HRP) or lucifer yellow CH (LY) and their labeled processes were traced to the utricular macula. For most labeled neurons, the discharge regularity, background discharge, and sensitivity to externally applied galvanic currents were determined, as were the gain (g2 Hz) and phase (phi 2 Hz) of the response to 2-Hz sinusoidal linear forces. Terminal fields were reconstructed and fibers were classified as calyx (n = 13) or dimorphic units (n = 40). No bouton units were recovered. Calyx units were confined to the striola. Dimorphic units were located in the striola (n = 8), the juxtastriola (n = 7), or the peripheral extrastriola (n = 25). 2. To determine whether the intra-axonal sample was representative, the physiological properties of labeled utricular units were compared with those of a larger sample of extracellularly recorded units. A comparison was also made between the morphology of intra-axonally labeled units and those labeled by the extracellular injection of HRP into the vestibular nerve. Most of the discrepancies between the intra-axonal and either extracellular sample can be explained by assuming that small-diameter fibers are underrepresented in the former sample. Dimorphic fibers labeled intra-axonally had more bouton endings and larger terminal trees than did those labeled extracellularly. The latter differences may reflect a sampling bias in the extracellular material. 3. Calyx units were irregularly discharging. The discharge regularity of dimorphic units was related to their macular locations. Only 1/8 dimorphic units in the striola was regularly discharging. The ratio increases to 3/7 in the juxtastriola and to 23/25 in the peripheral extrastriola. Among dimorphic units, there is a tendency for irregularly discharging afferents to have fewer bouton endings. The trend is far from perfect because it is possible to pick a subsample of dimorphic units that have similar numbers of boutons and, yet, have discharge patterns that range from regular to irregular. 4. Published morphological polarization maps can be used to predict the excitatory tilt directions of a unit from its macular location. Predictions were confirmed in 39/41 labeled afferents. 5. The galvanic sensitivity (beta *) of an afferent, irrespective of its peripheral innervation pattern or its epithelial location, was strongly correlated with a normalized coefficient of variation (CV*).(ABSTRACT TRUNCATED AT 400 WORDS)

Measurements from the 1-4-mm basal region of the chinchilla cochlea indicate the basilar membrane in the hook region (12-18 kHz) vibrates essentially as it does more apically, in the 5-9-kHz region. That is, a compressive nonlinearity in the region of the characteristic frequency, amplitude-dependent phase changes, and a gain relative to stapes motion that can attain nearly 10,000 at low levels. The displacement at threshold for auditory-nerve fibers in this region (20 dB SPL) was approximately 2 nm. Measurements were made at several locations in individual animals in the longitudinal and radial directions. The results indicate that there is little variability in the phase of motion radially and no indication of higher-order modes of vibration. The data from the longitudinal studies indicate that there is a shift in the location of the maximum with increasing stimulus levels toward the base. The cochlear amplifier extends over a 2-3-mm region around the location of the characteristic frequency.

The availability of transgenic and mutant lines makes the mouse a valuable model for study of the inner ear, and a powerful window into cochlear function can be obtained by recordings from single auditory nerve (AN) fibers. This study provides the first systematic description of spontaneous and sound-evoked discharge properties of AN fibers in mouse, specifically in CBA/CaJ and C57BL/6 strains, both commonly used in auditory research. Response properties of 196 AN fibers from CBA/CaJ and 58 from C57BL/6 were analyzed, including spontaneous rates (SR), tuning curves, rate versus level functions, dynamic range, response adaptation, phase-locking, and the relation between SR and these response properties. The only significant interstrain difference was the elevation of high-frequency thresholds in C57BL/6. In general, mouse AN fibers showed similar responses to other mammals: sharpness of tuning increased with characteristic frequency, which ranged from 2.5 to 70 kHz; SRs ranged from 0 to 120 sp/s, and fibers with low SR (<1 sp/s) had higher thresholds, and wider dynamic ranges than fibers with high SR. Dynamic ranges for mouse high-SR fibers were smaller (<20 dB) than those seen in other mammals. Phase-locking was seen for tone frequencies <4 kHz. Maximum synchronization indices were lower than those in cat but similar to those found in guinea pig.

Basilar-membrane responses to clicks were measured, using laser velocimetry, at a site of the chinchilla cochlea located about 3.5 mm from the oval window (characteristic frequency or CF: typically 8-10 kHz). They consisted of relatively undamped oscillations with instantaneous frequency that increased rapidly (time constant: 200 microseconds) from a few kHz to CF. Such frequency modulation was evident regardless of stimulus level and was also present post-mortem. Responses grew linearly at low stimulus levels, but exhibited a compressive nonlinearity at higher levels. Velocity-intensity functions were almost linear near response onset but became nonlinear within 100 microseconds. Slopes could be as low as 0.1-0.2 dB/dB at later times. Hence, the response envelopes became increasingly skewed at higher stimulus levels, with their center of gravity shifting to earlier times. The phases of near-CF response components changed by nearly 180 degrees as a function of time. At high stimulus levels, this generated cancellation notches and phase jumps in the frequency spectra. With increases in click level, sharpness of tuning deteriorated and the spectral maximum shifted to lower frequencies. Response phases also changed as a function of increasing stimulus intensity, exhibiting relative lags and leads at frequencies somewhat lower and higher than CF, respectively. In most respects, the magnitude and phase frequency spectra of responses to clicks closely resembled those of responses to tones. Post-mortem responses were similar to in vivo responses to very intense clicks.

The present study examined the morphological cell types of neurons labeled with intracellular horseradish peroxidase injections, many of them following electrophysiological recordings in the cochlear nucleus of gerbils and chinchillas. Most of the subdivisions and neuronal types previously described in the cat were identified in the present material, including spherical and globular bushy cells, stellate, bushy multipolar, elongate, octopus, and giant cells in the ventral cochlear nucleus, and a cartwheel cell in the dorsal cochlear nucleus. In many cases these structurally distinct neurons were correlated with their characteristic responses to stimulation by sound or intracellular injection of depolarizing current. The dendritic terminals of the elongate, antenniform, and clavate cells of the posteroventral cochlear nucleus link each of these cell types with neighboring structures in distinct patterns, which may provide a basis for differences in synaptic organization. These cell types differ from each other and from the stellate cells of the anteroventral cochlear nucleus. Despite their heterogeneous morphology, most of these neurons had a regular discharge in response to stimulation (choppers). Irregularly firing neurons (primary-like) had very different structures, e.g., the spherical and globular bushy cells and the bushy multipolar neuron. They, too, represent a heterogeneous population. An onset neuron was identified as an octopus cell. This paper compares the morphological observations with the electrophysiological properties of different cell types reported in a companion paper (Feng et al.[1994] J. Comp. Neurol.). Together, these findings imply that response properties may be partially independent of neuronal structure. Morphologically distinct neurons can generate similar temporal patterns in response to simple acoustic stimuli. Nevertheless, the synaptic organization of these different neuron types, including their connections, would be expected to affect or alter the cells' responses to appropriate stimuli. The possibility is raised that membrane properties and synaptic organization complement and interact with each other.