Mechanical bases of frequency tuning and neural excitation at the base of the cochlea: comparison of basilar-membrane vibrations and auditory-nerve-fiber responses in chinchilla.

We review the mechanical origin of auditory-nerve excitation, focusing on comparisons of the magnitudes and phases of basilar-membrane (BM) vibrations and auditory-nerve fiber responses to tones at a basal site of the chinchilla cochlea with characteristic frequency approximately 9 kHz located 3.5 mm from the oval window. At this location, characteristic frequency thresholds of fibers with high spontaneous activity correspond to magnitudes of BM displacement or velocity in the order of 1 nm or 50 microm/s. Over a wide range of stimulus frequencies, neural thresholds are not determined solely by BM displacement but rather by a function of both displacement and velocity. Near-threshold, auditory-nerve responses to low-frequency tones are synchronous with peak BM velocity toward scala tympani but at 80-90 dB sound pressure level (in decibels relative to 20 microPascals) and at 100-110 dB sound pressure level responses undergo two large phase shifts approaching 180 degrees. These drastic phase changes have no counterparts in BM vibrations. Thus, although at threshold levels the encoding of BM vibrations into spike trains appears to involve only relatively minor signal transformations, the polarity of auditory-nerve responses does not conform with traditional views of how BM vibrations are transmitted to the inner hair cells. The response polarity at threshold levels, as well as the intensity-dependent phase changes, apparently reflect micromechanical interactions between the organ of Corti, the tectorial membrane and the subtectorial fluid, and/or electrical and synaptic processes at the inner hair cells.

Frequency tuning of basilar membrane and auditory nerve fibers in the same cochleae.

Responses to tones of a basilar membrane site and of auditory nerve fibers innervating neighboring inner hair cells were recorded in the same cochleae in chinchillas. At near-threshold stimulus levels, the frequency tuning of auditory nerve fibers closely paralleled that of basilar membrane displacement modified by high-pass filtering, indicating that only relatively minor signal transformations intervene between mechanical vibration and auditory nerve excitation. This finding establishes that cochlear frequency selectivity in chinchillas (and probably in mammals in general) is fully expressed in the vibrations of the basilar membrane and renders unnecessary additional ("second") filters, such as those present in the hair cells of the cochleae of reptiles.

Basilar-membrane responses to clicks at the base of the chinchilla cochlea.

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.

Basilar-membrane responses to tones at the base of the chinchilla cochlea.

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.

Auditory-nerve fiber representation of temporal cues to voicing in word-medial stop consonants.

The length of the interval between the onset of consonant closure and the onset of voicing in a following vowel is a temporal cue that may distinguish between consonants /d/ and /t/ in word-medial environments; this interval has been called the "consonant duration" [V. W. Zue and M. Laferriere, J. Acoust. Soc. Am. 66, 1039-1050 (1979); S. Davis and W. V. Summers, J. Phon. 17, 339-353 (1989)]. The representation of this cue in the discharge patterns of chinchilla auditory-nerve fibers was measured. The two-syllable utterances /ida/, /ita/, /uda/, and /uta/ were recorded by one male and one female talker. The onset of consonant closure produced discharge rate decreases in nearly all neurons. Either the release of closure or the onset of voicing for the second vowel could elicit an increase in discharge rate. The latencies of these discharge rate changes varied across populations of neurons. A neural measure of consonant duration was extracted from the pattern of latencies. The "encoded duration" was longer for utterances with a medial /t/ than for utterances with a medial /d/. For each utterance the encoded duration increased with increases in characteristic frequency. The variability of the encoded duration measure was small enough to preserve the distinction between utterances with different word-medial consonants. The variability of the encoded duration was large, relative to the acoustic differences between utterances that included the same medial consonant. This pattern of variability could contribute to the formation of perceptual categories by reducing the audibility of within-category acoustic differences.

Chronic ethanol consumption causes increased glucuronidation of morphine in rabbits.

1. Male rabbits were given an i.p. injection of 15 mg/kg morphine and plasma concentrations of morphine and morphine-3-glucuronide (M3G) were simultaneously quantified by h.p.l.c. After 14 days of 10% ethanol in the rabbits' drinking water, a second injection of morphine was administered and plasma concentrations were determined again. 2. Morphine plasma clearance increased significantly by 42% after ethanol treatment. The area under the plasma concentration time curve (AUC) for morphine decreased by 23% while the AUC for the glucuronide increased by 22%. 3. The ratio of the AUCs (glucruonide/morphine) increased by 72%. These results demonstrate that chronic ethanol treatment of rabbits results in increased clearance of morphine after an i.p. dose. The increase in clearance is most likely due to induction of UDP-glucuronosyltransferase isozymes by ethanol.